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December 13, 2022

Progress toward an eventual HIV vaccine

At a glance.

• An experimental HIV vaccine elicited broadly neutralizing antibody precursors in people.
• With further development, the approach could lead to an effective vaccine strategy for HIV and AIDS.

More than 1 million new HIV infections occur each year. Ending the global HIV/AIDS pandemic will require an effective HIV vaccine. Vaccines work by inducing the immune system to make antibodies that can neutralize a particular pathogen. But doing so for HIV has been challenging because there are countless variants worldwide, and the immune system doesn’t normally make antibodies that can protect against a wide range of them. 

More than a decade ago , researchers at the Vaccine Research Center of NIH’s National Institute of Allergy and Infectious Diseases discovered a class of rare antibodies called broadly neutralizing antibodies (bnAbs) against HIV. These could neutralize many HIV strains at once. The bnAbs have been shown to prevent HIV infection in animals and humans. But inducing bnAbs with a vaccine has proven difficult. This is because bnAb-precursor B cells—the immune cells that develop into bnAb-producing B cells—are only rarely activated by the envelope proteins that form a protective coating for HIV.

One strategy to produce bnAbs involves specifically stimulating these rare precursor B cells. To do this, researchers led by Dr. William Schief at the Scripps Research Institute engineered a molecule based on a region of the HIV envelope protein called the CD4 binding site. They developed a modified protein to prime the precursor B cells to react. The protein, called eOD-GT8, was designed to incorporate into a self-assembling nanoparticle with 60 copies. The nanoparticle vaccine was previously shown to induce production of bnAb precursors in mice.

Based on this evidence, a research team led by Drs. Juliana McElrath at the Fred Hutchinson Cancer Center, Adrian McDermott at NIH’s Vaccine Research Center, and Schief conducted a phase 1 clinical trial of the eOD-GT8 vaccine to begin assessing its safety and efficacy in people. Results appeared in Science on December 2, 2022.

Forty-eight participants were immunized with either a low or high dose of the vaccine or a placebo. Immunization consisted of two doses, given eight weeks apart. The vaccine had a favorable safety profile, with no serious adverse events reported.

Before and after vaccination, the researchers measured the presence in participants’ blood and lymph nodes of bnAb-precursor B cells targeting eOD-GT8. They found that these cells increased in 97% of vaccine recipients after at least one of the two doses. Frequencies of these B cells increased by more than 500-fold compared to before vaccination. 

The team also examined the receptors that B cells use to recognize pathogens. These receptors resemble antibodies and recognize their targets in a similar way. Receptors on the eOD-GT8-targeting bnAb-precursor B cells shared several molecular features with bnAbs. The team also saw early steps in the development of bnAbs. These include an increase in mutations in the receptor genes after the second vaccine dose and an increase in the affinity of the receptors for the vaccine.

These findings establish proof of concept and a crucial first step for the strategy of eliciting bnAbs against HIV. But this priming vaccine alone cannot induce production of mature bnAbs. Booster vaccines will be needed to elicit bnAb production and protection against HIV. The results support further development of such boosters.

“This trial and additional analyses will help inform design of the remaining stages of a candidate HIV vaccine regimen—while also enabling others in the field to develop vaccine strategies for additional viruses,” McElrath says.

—by Brian Doctrow, Ph.D.

Related Links

• “Slow” Vaccine Delivery Improves Immune Response To HIV
• Combination Antibody Treatment For HIV
• Experimental mRNA HIV Vaccine Shows Promise in Animals
• Antibody Combination Suppresses HIV
• Test Vaccine Active Against Many HIV Strains
• Engineered Antibody Protects Monkeys From HIV-Like Virus
• HIV Vaccine Progress in Animal Studies
• Antibodies Protect Human Cells from Most HIV Strains
• HIV and AIDS: Know the Facts

References:  Vaccination induces HIV broadly neutralizing antibody precursors in humans. Leggat DJ, Cohen KW, Willis JR, Fulp WJ, deCamp AC, Kalyuzhniy O, Cottrell CA, Menis S, Finak G, Ballweber-Fleming L, Srikanth A, Plyler JR, Schiffner T, Liguori A, Rahaman F, Lombardo A, Philiponis V, Whaley RE, Seese A, Brand J, Ruppel AM, Hoyland W, Yates NL, Williams LD, Greene K, Gao H, Mahoney CR, Corcoran MM, Cagigi A, Taylor A, Brown DM, Ambrozak DR, Sincomb T, Hu X, Tingle R, Georgeson E, Eskandarzadeh S, Alavi N, Lu D, Mullen TM, Kubitz M, Groschel B, Maenza J, Kolokythas O, Khati N, Bethony J, Crotty S, Roederer M, Karlsson Hedestam GB, Tomaras GD, Montefiori D, Diemert D, Koup RA, Laufer DS, McElrath MJ, McDermott AB, Schief WR. Science . 2022 Dec 2;378(6623):eadd6502. doi: 10.1126/science.add6502. Epub 2022 Dec 2. PMID: 36454825.

Funding:  NIH’s National Institute of Allergy and Infectious Diseases (NIAID); International AIDS Vaccine Initiative (IAVI); Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery; Swedish Research Council; Ragon Institute of MGH, MIT, and Harvard.

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After decades of failures, researchers have renewed hopes for an effective HIV vaccine

The world needs an HIV vaccine if it ever hopes to beat a virus that still infects over 1 million people a year and contributes to hundreds of thousands of deaths.

Despite 20 years of failures in major HIV vaccine trials — four this decade alone — researchers say recent scientific advances have likely, hopefully, put them on the right track to develop a highly effective vaccine against the insidious virus.

But probably not until the 2030s. 

“An effective vaccine is really the only way to provide long-term immunity against HIV, and that’s what we need,” Dr. Julie McElrath, the director of the vaccine and infectious disease division at the Fred Hutchinson Cancer Center in Seattle, said Monday at the Conference on Retroviruses and Opportunistic Infections in Denver.

All current HIV vaccine action is in the laboratory, animal studies or very early human trials.

Researchers at the retrovirus conference presented favorable results from two HIV vaccine studies. One found that a modification to the simian version of HIV spurred production of what are known as broadly neutralizing antibodies against the virus in monkeys. Another showed promise in the effort to coax the immune system’s B cells to make the powerful antibodies in humans. 

“These trials illustrate as a proof of concept that we can train the immune system. But we need to further optimize it and test it in clinical trials,” Karlijn van der Straten, a Ph.D. student at the Academic Medical Center at Amsterdam University, who presented the human study, said at a news conference Monday.

Still, the scrappy scientists in this field face a towering challenge. HIV is perhaps the most complex pathogen ever known. 

“The whole field has learned from the past,” said William Schief, who leads Moderna’s HIV vaccine efforts. “We’ve learned strategies that don’t work.”

The cost has already been immense. Nearly $17 billion was spent worldwide on HIV -vaccine research from 2000 to 2021. Nearly $1 billion more is spent annually, according to the Joint United Nations Program on HIV/AIDS and the nonprofit HIV group AVAC.

“Maintaining the funding for HIV vaccines right now is really important,” said Dr. Nina Russell, who directs HIV research at the Bill & Melinda Gates Foundation. She pointed to the field’s own “progress and the excitement” and to how “HIV vaccine science and scientists continue to drive innovation and science that benefits other infectious diseases and global health in general.” 

Case in point: Covid. Thanks to HIV research, the mRNA vaccine technology was already available in 2020 to speed a coronavirus vaccine to market.

Why the HIV vaccine efficacy trials failed

In strong contrast to Covid, the HIV vaccine endeavor has spanned four decades. Only one of the nine HIV vaccine trials have shown efficacy: a trial conducted in Thailand and published in 2009 that reported a modest 31% reduction in HIV risk.

HIV vaccine researchers subsequently spent years seeking to retool and improve that vaccine strategy, leading to a series of trials that launched in the late 2010s — only to fail.

Researchers have concluded those latest trials were doomed because, aside from prompting an anti-HIV response based in immune cells, they only drove the immune system to produce what are known as non-neutralizing antibodies. Those weapons just weren’t strong enough for such a fearsome foe.

Preventing HIV through vaccination remains a daunting challenge because the immune system doesn’t naturally mount an effective defense against the virus, as it does with so many other vaccine-preventable infections, including Covid. An HIV vaccine must coax from the body a supercharged immune response with no natural equivalent.

That path to victory is based on a crucial caveat: A small proportion of people with HIV do produce what are known as broadly neutralizing antibodies against the virus. They attack HIV in multiple ways and can neutralize a swath of variants of the virus.

Those antibodies don’t do much apparent good for people who develop them naturally, because they typically don’t arise until years into infection. HIV establishes a permanent reservoir in the body within about a week after infection, one that their immune response can’t eliminate. So HIV-positive people with such antibodies still require antiretroviral treatment to remain healthy.

Researchers believe that broadly neutralizing antibodies could prevent HIV from ever seeding an infection, provided the defense was ready in advance of exposure. A pair of major efficacy trials, published in 2021 , demonstrated that infusions of cloned versions of one such antibody did, indeed, protect people who were exposed to certain HIV strains that are susceptible to that antibody. 

However, globally, those particular strains of the virus comprise only a small subset of all circulating HIV. That means researchers can’t simply prompt a vaccine to produce that one antibody and expect it to be effective. Importantly, from this study they got a sense of what antibody level would be required to prevent infection. 

It’s a high benchmark, but at least investigators now have a clearer sense of the challenge before them. 

Also frustrating the HIV vaccine quest is that the virus mutates like mad. Whatever spot on the surface of the virus that antibodies target might be prone to change through mutation, thus allowing the virus to evade their attack. Consequently, researchers search for targets on the virus’ surface that aren’t highly subject to mutation.

Experts also believe warding off the mutation threat will require targeting multiple sites on the virus. So researchers are seeking to develop a portfolio of immune system prompts that would spur production of an array of broadly neutralizing antibodies.

Prompting the development of such antibodies requires a complex, step-by step process of coaxing the infection-fighting B cells, getting them to multiply and then guiding their maturation into potent broadly neutralizing antibody-producing factories.

HIV vaccine development ‘in a better place’

Dr. Carl Dieffenbach, the head of the AIDS division at the National Institute of Allergy and Infectious Diseases, said numerous recent technological advances — including mRNA, better animal models of HIV infection and high-tech imaging technology — have improved researchers’ precision in designing, and speed in producing, new proteins to spur anti-HIV immune responses.

Global collaboration among major players is also flourishing, researchers said. There are several early-stage human clinical trials of HIV-vaccine components underway.

Three mRNA- based early human trials of such components have been launched since 2022. Among them, they have been led or otherwise funded by the global vaccine research nonprofit group IAVI, Fred Hutch, Moderna, Scripps Research, the Gates Foundation, the National Institutes of Health, the U.S. Agency for International Development, and university teams. More such trials are in the works.

On Friday, Science magazine reported concerning recent findings that among the three mRNA trials, a substantial proportion of participants — 7% to 18%, IAVI said in a statement — experienced skin-related symptoms following injections, including hives, itching and welts.

IAVI said in its statement that it and partners are investigating the HIV trials’ skin-related outcomes, most of which were “mild or moderate and managed with simple allergy medications.” 

Researchers have shown success in one of those mRNA trials in executing a particular step in the B-cell cultivation process.

That vaccine component also generated “helper” CD4 cells primed to combat HIV. The immune cells are expected to operate like an orchestra conductor for the immune system, coordinating a response by sending instructions to B cells and scaling up other facets of an assault on HIV.

A complementary strategy under investigation seeks to promote the development of “killer” CD8 cells that might be primed to kill off any immune cells that the antibodies failed to save from infection.

Crucially, investigators believe they are now much better able to discern top vaccine component candidates from the duds. They plan to spend the coming years developing such components so that when they do assemble the most promising among them into a multi-pronged vaccine, they can be much more confident of ultimate success in a trial.

“An HIV vaccine could end HIV,” McElrath said at the Denver conference. “So I say, ‘Let’s just get on with it.”

Dr. Mark Feinberg, president and CEO of IAVI, suggested that the first trial to test effectiveness of the vaccine might not launch until 2030 or later.

Even so, he was bullish.

“The field of HIV vaccine development is in a better place now than it’s ever been,” he said.

Benjamin Ryan is independent journalist specializing in science and LGBTQ coverage. He contributes to NBC News, The New York Times, The Guardian and Thomson Reuters Foundation and has also written for The Washington Post, The Nation, The Atlantic and New York.

Perceptions and Acceptance of a Prophylactic Vaccine for Human Immunodeficiency Virus (HIV): A Qualitative Study

Affiliations.

• 1 Clinical Outcomes Assessment, Clarivate, London, UK. [email protected].
• 2 Janssen Global Services LLC, Raritan, NJ, USA.
• 3 Clinical Outcomes Assessment, Clarivate, London, UK.
• 4 Janssen Vaccines and Prevention B.V., Leiden, The Netherlands.
• PMID: 38581599
• DOI: 10.1007/s40271-024-00686-7

Background: Despite advances in human immunodeficiency virus (HIV) prevention methods, such as the advent of pre-exposure prophylaxis (PrEP), the number of people with newly acquired HIV remains high, particularly in at-risk groups. A prophylactic HIV vaccine could contribute to reduced disease prevalence and future transmission and address limitations of existing options, such as suboptimal long-term adherence to PrEPs.

Methods: This qualitative study aimed to capture perceptions towards and acceptance of prophylactic HIV vaccination in three adult populations in the United States: the general population, 'at-risk' individuals (e.g. men who have sex with men, transgender individuals, gender-nonconforming individuals, and individuals in a sexual relationship with a person living with HIV), and parents/caregivers of children aged 9-17 years. Interviews were conducted with 55 participants to explore key drivers and barriers to HIV vaccine uptake, and a conceptual model was developed.

Results: The sample was diverse; participants were 51% female, aged 20-57 years (mean 37 years), 33% with high school diploma as highest education level, and identified as White (42%), Black or African American (35%), of Hispanic, Latino, or Spanish origin (22%), or other races/ethnicities (8%) [groupings are not mutually exclusive]. Perceptions were influenced by individual, interpersonal, community, institutional, and structural factors. Overall, 98% of participants thought vaccination would be beneficial in preventing HIV. Key considerations/barriers included perceived susceptibility, i.e. whether participants felt there was a risk of contracting HIV (discussed by 90%); the clinical profile of the vaccine (e.g. the adverse effect profile [98%], and vaccine efficacy [85%], cost [73%] and administration schedule [88%]); and concerns around potential vaccine-induced seropositivity (VISP; 62%). Stigma was not found to be an important barrier, with a general view that vaccination status was personal. Participants in the 'at-risk' group were the most likely to accept an HIV vaccine (70%). Unique concerns in the subgroups included how a potential vaccine's clinical profile compared with PrEP, voiced by those receiving/considering PrEP, and considerations of children's views on the topic, voiced by parents/caregivers.

Conclusions: Understanding these factors could help develop HIV vaccine research strategies and contribute toward public health messaging to support future HIV vaccination programs.

© 2024. The Author(s).

COVID-19 Vaccine Hesitancy Among People Living with HIV: A Systematic Review and Meta-Analysis

• Substantive Review
• Published: 16 April 2024

Cite this article

• Xin Liu 1   na1 ,
• Yijin Wu 1   na1 ,
• Zhenyu Huo 2 ,
• Ling Zhang 1 ,
• Shu Jing 1 ,
• Zhenwei Dai 1 ,
• Yiman Huang 1 ,
• Mingyu Si 1 ,
• You Xin 1 ,
• Yimin Qu 1 ,
• Shenglan Tang 3 &
• Xiaoyou Su   ORCID: orcid.org/0000-0002-4216-2142 1  

Vaccine hesitancy is one of the top 10 threats to global health, which affects the prevalence and fatality of vaccine-preventable diseases over the world. During the COVID-19 pandemic, people living with HIV (PLWH) may have higher risks of infection, more serious complications, and worse prognosis without the protection of the COVID-19 vaccine. A systematic review and meta-analysis aiming to evaluate the prevalence of COVID-19 vaccine hesitancy among PLWH was conducted using PubMed, Embase, and Web of Science databases for studies published between January 1, 2020, and August 31, 2022. The pooled prevalence with a corresponding 95%CI of COVID-19 vaccine hesitancy among PLWH was reported. Subgroup analysis was conducted to explore variation in prevalence across different categories. 23 studies with a total of 19,922 PLWH were included in this study. The prevalence of COVID-19 vaccine hesitancy among PLWH was 34.0%, and the influencing factors included male, influenza vaccination experience, and a CD4 count of more than 200 cells/mm 3 . Subgroup analysis did not identify significant causes of heterogeneity but showed that the prevalence of COVID-19 vaccine hesitancy among PLWH varies by study period, region, and race. Although all PLWH are recommended to receive the COVID-19 vaccine, a large proportion of them remain hesitant to be vaccinated. Therefore, governments and relevant institutions should take specific measures to encourage and promote vaccination to improve the coverage of the COVID-19 vaccine among PLWH.

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Data Availability

The study protocol is publicly available at PROSPERO, CRD42022350187. The data used for this meta-analysis will be made available on request to the corresponding author.

WHO. WHO Director-General’s opening remarks at the media briefing on COVID-19 2020 [cited 2022 21 December]; https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 .

WHO. Global excess deaths associated with COVID-19 (modelled estimates). 2022 5 May 2022 [cited 2022 25 December]; https://www.who.int/data/sets/global-excess-deaths-associated-with-covid-19-modelled-estimates .

Kolahchi Z, De Domenico M, Uddin LQ, et al. COVID-19 and its global economic impact. Adv Exp Med Biol. 2021;1318:825–37.

Article   CAS   PubMed   Google Scholar  

Mathieu E, Ritchie H, Ortiz-Ospina E, et al. A global database of COVID-19 vaccinations. Nat Hum Behav. 2021;5(7):947–53.

Article   PubMed   Google Scholar  

Britton T, Ball F, Trapman P. A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2. Science. 2020;369(6505):846–9.

Article   CAS   PubMed   PubMed Central   Google Scholar  

WHO. Strategy to Achieve Global Covid-19 Vaccination by mid-2022. 2021 [cited 2022 25 December]; https://cdn.who.int/media/docs/default-source/immunization/covid-19/strategy-to-achieve-global-covid-19-vaccination-by-mid-2022.pdf?sfvrsn=5a68433c_5 .

Edouard Mathieu HR, Rodés-Guirao L, Appel C, Giattino C, Hasell J. Bobbie Macdonald, Saloni Dattani, Diana Beltekian, Esteban Ortiz-Ospina, Max Roser Coronavirus Pandemic (COVID-19) . 2020: OurWorldInData.org.

MacDonald NE. Vaccine hesitancy: definition, scope and determinants. Vaccine. 2015;33(34):4161–4.

WHO. Ten Treats to Global Health in 2019 2019 [cited 2022 25 December]; https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019 .

Ball P. Anti-vaccine movement could undermine efforts to end coronavirus pandemic, researchers warn. Nature. 2020;581(7808):251.

Wang Y, Xie Y, Hu S, et al. Systematic review and Meta-analyses of the Interaction between HIV infection and COVID-19: two years’ evidence Summary. Front Immunol. 2022;13:864838.

Diseases WCDoHicwtNIfC. Risk factors for Coronavirus Disease 2019 (COVID-19) death in a Population Cohort Study from the Western Cape Province, South Africa. Clin Infect Dis. 2021;73(7):e2005–15.

Article   Google Scholar  

Council G. W.G.o.t.N.O.o.A.R.A. Guidelines Working Groups of the NIH Office of AIDS Research Advisory Council. Guidance for COVID-19 and People with HIV. 2022 [cited 2022 25 December]; https://clinicalinfo.hiv.gov/en/guidelines/guidance-covid-19-and-people-hiv/whats-new-covid-19-and-hiv-guidance .

Cascini F, Pantovic A, Al-Ajlouni Y, Failla G, Ricciardi W. Attitudes, acceptance and hesitancy among the general population worldwide to receive the COVID-19 vaccines and their contributing factors: a systematic review. EClinicalMedicine. 2021;40:101113.

Article   PubMed   PubMed Central   Google Scholar  

Bogart LM, Ojikutu BO, Tyagi K, et al. COVID-19 Related Medical Mistrust, Health impacts, and potential vaccine hesitancy among Black americans Living with HIV. J Acquir Immune Defic Syndr. 2021;86(2):200–7.

Kaida A, Brotto LA, Murray MCM, et al. Intention to receive a COVID-19 vaccine by HIV Status among a Population-based sample of women and gender diverse individuals in British Columbia, Canada. AIDS Behav. 2022;26(7):2242–55.

West S, King V, Carey TS et al. Systems to rate the strength of scientific evidence. Evid Rep Technol Assess (Summ), 2002(47): p. 1–11.

Zhao H, Wang H, Li H, et al. Uptake and adverse reactions of COVID-19 vaccination among people living with HIV in China: a case-control study. Hum Vaccin Immunother. 2021;17(12):4964–70.

Vallée A, Fourn E, Majerholc C, Touche P, Zucman D. COVID-19 vaccine hesitancy among French people living with HIV. Vaccines (Basel), 2021. 9(4).

Swendeman D, Norwood P, Saleska J, et al. Vaccine attitudes and COVID-19 vaccine intentions and Prevention behaviors among Young people At-Risk for and living with HIV in Los Angeles and New Orleans. Volume 10. Vaccines (Basel); 2022. 3.

Shrestha R, Meyer JP, Shenoi S et al. COVID-19 vaccine hesitancy and Associated Factors among people with HIV in the United States: findings from a National Survey. Vaccines (Basel), 2022. 10(3).

Qi L, Yang L, Ge J, Yu L, Li X. COVID-19 vaccination behavior of people living with HIV: the mediating role of Perceived Risk and Vaccination Intention. Vaccines (Basel), 2021. 9(11).

Ortiz-Martínez Y, López-López M, Ruiz-González CE, et al. Willingness to receive COVID-19 vaccination in people living with HIV/AIDS from Latin America. Int J STD AIDS. 2022;33(7):652–9.

Menza TW, Capizzi J, Zlot AI, Barber M, Bush L. COVID-19 vaccine uptake among people living with HIV. AIDS Behav. 2022;26(7):2224–8.

Jones DL, Salazar AS, Rodriguez VJ, et al. Severe Acute Respiratory Syndrome Coronavirus 2: vaccine hesitancy among underrepresented racial and ethnic groups with HIV in Miami, Florida. Open Forum Infect Dis. 2021;8(6):ofab154.

Huang X, Yu M, Fu G, et al. Willingness to receive COVID-19 vaccination among people living with HIV and AIDS in China: Nationwide cross-sectional online survey. JMIR Public Health Surveill. 2021;7(10):e31125.

Govere-Hwenje S, Jarolimova J, Yan J, et al. Willingness to accept COVID-19 vaccination among people living with HIV in a high HIV prevalence community. BMC Public Health. 2022;22(1):1239.

Ekstrand ML, Heylen E, Gandhi M, et al. COVID-19 vaccine hesitancy among PLWH in South India: implications for Vaccination campaigns. J Acquir Immune Defic Syndr. 2021;88(5):421–5.

Liu Y, Han J, Li X et al. COVID-19 vaccination in people living with HIV (PLWH) in China: A Cross Sectional Study of Vaccine Hesitancy, Safety, and immunogenicity. Vaccines (Basel), 2021. 9(12).

Strathdee SA, Abramovitz D, Harvey-Vera A, et al. Correlates of Coronavirus Disease 2019 (COVID-19) vaccine hesitancy among people who inject drugs in the San Diego-Tijuana Border Region. Clin Infect Dis. 2022;75(1):e726–33.

Jaiswal J, Krause KD, Martino RJ, et al. SARS-CoV-2 vaccination hesitancy and behaviors in a National Sample of people living with HIV. AIDS Patient Care STDS. 2022;36(1):34–44.

Davtyan M, Frederick T, Taylor J, et al. Determinants of COVID-19 vaccine acceptability among older adults living with HIV. Med (Baltim). 2022;101(31):e29907.

Article   CAS   Google Scholar  

Holt M, MacGibbon J, Bavinton B, et al. COVID-19 vaccination uptake and hesitancy in a National Sample of Australian Gay and Bisexual men. AIDS Behav. 2022;26(8):2531–8.

Ousseine YM, Vaux S, Vandentorren S et al. Predictors of uncertainty and unwillingness to receive the COVID-19 vaccine in men who have sex with men in France. Int J Environ Res Public Health, 2022. 19(9).

Su J, Jia Z, Wang X, et al. Acceptance of COVID-19 vaccination and influencing factors among people living with HIV in Guangxi, China: a cross-sectional survey. BMC Infect Dis. 2022;22(1):471.

Wickersham JA, Meyer JP, Shenoi S, et al. Willingness to be vaccinated against COVID-19 among people with HIV in the United States: results from a National Survey. Front Med (Lausanne). 2022;9:886936.

Wu S, Ming F, Xing Z, et al. COVID-19 vaccination willingness among people living with HIV in Wuhan, China. Front Public Health. 2022;10:883453.

Iliyasu Z, Kwaku AA, Umar AA, et al. Predictors of COVID-19 vaccine acceptability among patients living with HIV in Northern Nigeria: a mixed methods study. Curr HIV Res. 2022;20(1):82–90.

Caserotti M, Girardi P, Rubaltelli E, et al. Associations of COVID-19 risk perception with vaccine hesitancy over time for Italian residents. Soc Sci Med. 2021;272:113688.

Tewarson H, Greene K, Fraser MR. State strategies for addressing barriers during the early US COVID-19 vaccination campaign. Am J Public Health. 2021;111(6):1073–7.

Jahani H, Chaleshtori AE, Khaksar SMS, Aghaie A, Sheu JB. COVID-19 vaccine distribution planning using a congested queuing system-A real case from Australia. Transp Res E Logist Transp Rev. 2022;163:102749.

Jilich D, Skrzat-Klapaczyńska A, Fleischhans L, et al. National strategies for vaccination against COVID-19 in people living with HIV in Central and Eastern European region. HIV Med. 2022;23(5):546–52.

Njoga EO, Awoyomi OJ, Onwumere-Idolor OS et al. Persisting vaccine hesitancy in Africa: the whys, Global Public Health Consequences and ways-Out-COVID-19 Vaccination Acceptance Rates as Case-in-point. Vaccines (Basel), 2022. 10(11).

Oyelade T, Alqahtani JS, Hjazi AM et al. Global and Regional Prevalence and outcomes of COVID-19 in people living with HIV: a systematic review and Meta-analysis. Trop Med Infect Dis, 2022. 7(2).

Marcos-Garcia P, Carmona-Moreno C, López-Puga J, Ruiz-Ruano AM, García. COVID-19 pandemic in Africa: is it time for water, sanitation and hygiene to climb up the ladder of global priorities? Sci Total Environ. 2021;791:148252.

Salyer SJ, Maeda J, Sembuche S, et al. The first and second waves of the COVID-19 pandemic in Africa: a cross-sectional study. Lancet. 2021;397(10281):1265–75.

McNeil A, Purdon C. Anxiety disorders, COVID-19 fear, and vaccine hesitancy. J Anxiety Disord. 2022;90:102598.

Hotez PJ. Anti-science extremism in America: escalating and globalizing. Microbes Infect. 2020;22(10):505–7.

Unroe KT, Evans R, Weaver L, Rusyniak D, Blackburn J. Willingness of Long-Term Care Staff to receive a COVID-19 vaccine: a single state survey. J Am Geriatr Soc. 2021;69(3):593–9.

Bailey ZD, Krieger N, Agénor M, et al. Structural racism and health inequities in the USA: evidence and interventions. Lancet. 2017;389(10077):1453–63.

Dada D, Djiometio JN, McFadden SM, et al. Strategies that promote equity in COVID-19 Vaccine Uptake for Black communities: a review. J Urban Health. 2022;99(1):15–27.

Syed U, Kapera O, Chandrasekhar A et al. The role of faith-based organizations in improving vaccination confidence & addressing vaccination disparities to help improve vaccine uptake: a systematic review. Vaccines (Basel), 2023. 11(2).

Abdul-Mutakabbir JC, Casey S, Jews V, et al. A three-tiered approach to address barriers to COVID-19 vaccine delivery in the black community. Lancet Glob Health. 2021;9(6):e749–50.

Meckiff BJ, Ramírez-Suástegui C, Fajardo V, et al. Imbalance of Regulatory and cytotoxic SARS-CoV-2-Reactive CD4(+) T cells in COVID-19. Cell. 2020;183(5):1340–e135316.

Frater J, Ewer KJ, Ogbe A, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial. Lancet HIV. 2021;8(8):e474–85.

Terry E, Cartledge S, Damery S, Greenfield S. Factors associated with COVID-19 vaccine intentions during the COVID-19 pandemic; a systematic review and meta-analysis of cross-sectional studies. BMC Public Health. 2022;22(1):1667.

Aw J, Seng JJB, Seah SSY, Low LL. COVID-19 vaccine Hesitancy-A Scoping Review of Literature in High-Income Countries. Vaccines (Basel), 2021. 9(8).

Oliver J, Kaufman J, Bagot K, et al. Drivers of COVID-19 vaccine hesitancy among women of childbearing age in Victoria, Australia: a descriptive qualitative study. Vaccine X. 2022;12:100240.

Milford C, Beksinska M, Greener R, et al. Fertility desires of people living with HIV: does the implementation of a sexual and reproductive health and HIV integration model change healthcare providers’ attitudes and clients’ desires? BMC Health Serv Res. 2021;21(1):509.

Ta Park VM, Dougan M, Meyer OL et al. Vaccine willingness: Findings from the COVID-19 effects on the mental and physical health of Asian Americans & Pacific Islanders survey study (COMPASS) Prev Med Rep, 2021. 23: p. 101480.

Toshkov D. Explaining the gender gap in COVID-19 vaccination attitudes. Eur J Public Health. 2023;33(3):490–5.

Daher M, Al Rifai M, Kherallah RY, et al. Gender disparities in difficulty accessing healthcare and cost-related medication non-adherence: the CDC behavioral risk factor surveillance system (BRFSS) survey. Prev Med. 2021;153:106779.

Courtenay WH. Constructions of masculinity and their influence on men’s well-being: a theory of gender and health. Soc Sci Med. 2000;50(10):1385–401.

Zhang C, McMahon J, Leblanc N, et al. Association of Medical Mistrust and Poor Communication with HIV-Related Health outcomes and Psychosocial Wellbeing among Heterosexual men living with HIV. AIDS Patient Care STDS. 2020;34(1):27–37.

Boschung K, Gill MJ, Krentz HB, et al. COVID-19 vaccine uptake among people with HIV: identifying characteristics associated with vaccine hesitancy. Sci Rep. 2023;13(1):20610.

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Acknowledgements

We thank Tianzuo Gao, Tianyou Zhao from Westlake Boys High School, New Zealand for their support with literature search of this work.

This study was funded by CAMS Innovation Fund for Medical Sciences (No. CAMS 2021- I2M-1-004) and Sanming Project of Medicine in Shenzhen (No. SZSM202211032).

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Xin Liu and Yijin Wu contributed Co-first authors.

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School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Xin Liu, Yijin Wu, Ling Zhang, Shu Jing, Zhenwei Dai, Yiman Huang, Mingyu Si, You Xin, Yimin Qu & Xiaoyou Su

State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Global Health Research Center, Duke Kunshan University, Jiangsu, China

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X.L. and Y.H. conceived the study and design the protocol. X.L., Y.W., S.J., and L.Z. conducted the study selection and extracted the data. X.L. and Z.H. did the statistical analysis. X.L., Y.W. did the quality assessment and wrote the original draft. Z.D., Y.X., Y.Q., S.T. and X.S. review and revise the paper, All authors contribute to writing and review of the article and approved the published version of the manuscript.

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Liu, X., Wu, Y., Huo, Z. et al. COVID-19 Vaccine Hesitancy Among People Living with HIV: A Systematic Review and Meta-Analysis. AIDS Behav (2024). https://doi.org/10.1007/s10461-024-04344-9

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HIV and SARS-CoV-2: Tracing a Path of Vaccine Research and Development

Brittany ober shepherd.

1 Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Suite 2A14, Silver Spring, MD 20910 USA

2 Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817 USA

David Chang

3 US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910 USA

Sandhya Vasan

Kayvon modjarrad, purpose of review.

This review examines the major advances and obstacles in the field of HIV vaccine research as they pertain to informing the development of vaccines against SARS-CoV-2.

Recent Findings

Although the field of HIV research has yet to deliver a licensed vaccine, the technologies developed and knowledge gained in basic scientific disciplines, translational research, and community engagement have positively impacted the development of vaccines for other viruses, most notably and recently for SARS-CoV-2. These advances include the advent of viral vectors and mRNA as vaccine delivery platforms; the use of structural biology for immunogen design; an emergence of novel adjuvant formulations; a more sophisticated understanding of viral phylogenetics; improvements in the development and harmonization of accurate assays for vaccine immunogenicity; and maturation of the fields of bioethics and community engagement for clinical trials conducted in diverse populations.

Decades of foundational research and investments into HIV biology, though yet to yield an authorized or approved vaccine for HIV/AIDS, have now paid dividends in the rapid development of safe and effective SARS-CoV-2 vaccines. This latter success presents an opportunity for feedback on improved pathways for development of safe and efficacious vaccines against HIV and other pathogens.

Introduction

The identification, in December 2019, of a novel human coronavirus, later labeled severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represented the beginning of one the greatest public health challenges the world has faced since the emergence of human immunodeficiency virus (HIV) four decades earlier. As the pandemic of coronavirus disease 2019 (COVID-19) has unfolded, the tools and knowledge gained in the 40-year fight against HIV and acquired immunodeficiency syndrome (AIDS) have been critical for the rapid development of reliable countermeasures against COVID-19, including several safe and effective vaccines.

Although a licensed vaccine has eluded the HIV research community, sustained investments into understanding the virus’s biology and its interaction with the human host have resulted in a combination of highly effective therapies and prevention modalities that have made significant inroads into the control of the AIDS pandemic. In contrast, the efforts to create an effective vaccine or definitive cure for HIV have been unsuccessful thus far. Nonetheless, global initiatives toward these ends have ushered in a period of creativity and coordination on a scale not seen before in the scientific and public health communities. The unprecedented speed with which SARS-CoV-2 prophylactic and treatment options have been made available to the public was built on this preceding era of innovation in response to HIV/AIDS. In this brief review, we highlight some of the most critical scientific advances and public health lessons gained in the endeavor for an HIV vaccine and trace their influence on the accelerated development of multiple COVID-19 vaccines.

Vaccine Platforms

The history of HIV vaccine development is punctuated by an alternating series of accomplishments and disappointments. Despite the inconsistency of major advances in the field, there has been continuous, steady progress in novel antigen delivery platforms, particularly in the form of genetic vaccines [ 1 , 2 ]. DNA, mRNA, and viral vectors—advanced to various stages of clinical evaluation prior to the COVID-19 pandemic—have the advantage of being scalable and customizable, allowing for facile modification to deliver antigens from different pathogens.

Viruses, by definition, can be reduced to self-replicating strings of nucleic acids encased in a protein coat that are dependent on host cell machinery to generate copies of themselves. The evolved properties that define the virus life cycle have been leveraged as an efficient means of delivering genetic sequences of antigens for endogenous production. Multiple virus families have been explored for their ability to serve as shuttles for antigenic sequences. In the context of HIV vaccine research, however, adenoviruses were identified early on as a promising platform to recruit both humoral and cellular arms of the immune response. Two types of adenoviruses, in particular, have been the focus of HIV vaccine platforms: an adenovirus that infects chimpanzees [ 3 , 4 ] and a specific but rare serotype that infects humans [ 5 ]. Both viruses have since been used as viral vectors for two SARS-CoV-2 vaccines that are currently in use worldwide (ChAdOx-1 nCoV-19 and Ad26.COV2.S) [ 6 , 7 ]. Although intended to be used as standalone monovalent vaccines against the wild-type virus, these platforms can be modified to address variants of concern either in homologous or heterologous prime-boost regimens to recall and potentiate a broader humoral and cell-mediated response against multiple SARS-CoV-2 strains.

Despite their success in reaching the commercial market for SARS-CoV-2, a rare risk of the adenovirus vector platform has since been revealed due to its administration to millions of people. The risk of coagulopathy from the platform, though serious, is so rare that it would never have been identified from the tens of thousands of individuals who had received the vaccine platform in the context of the more recent COVID-19 and prior HIV clinical trials. This newly identified side effect will likely influence the design and conduct of clinical trials with adenovirus vector vaccines for HIV and other pathogens going forward. The utility of adenovirus vaccines for HIV, however, remains unclear. Two efficacy trials, called Imbokodo (HVTN 705) and Mosaico (HVTN 706), are testing an approach that primes with the Ad26 vector containing mosaic inserts representing multiple HIV subtypes, followed by a protein boost, which also features a mosaic design. The Imbokodo trial demonstrated an efficacy of 25% with a confidence interval lower bound less than zero. The chimpanzee adenovirus ChAdOx1 is also being evaluated in a heterologous prime-boost strategy, but as a therapeutic vaccine series designed to control HIV-1 viral replication [ 8 ].

Perhaps even a greater leap forward in genetic vaccines has been for mRNA platforms, which, despite their more recent widespread recognition, have a history extending back decades [ 1 ]. Improvements in mRNA stability, delivery, and expression have been gradual and were made in the context of vaccine development for HIV and other emerging pathogens, such as the Zika virus. The progress, though incremental, was sufficient for the platform’s large-scale debut during the COVID-19 pandemic. As such, two highly effective mRNA vaccines have now received either FDA emergency authorization or full approval [ 9 , 10 ].

Structure-Based Approach to Antigen Design

The platform, though a critical component to any vaccine, is only one part of the product. The antigen that is presented on or delivered through any platform will dictate the specificity of the immune response and largely direct the durability and breadth of immunity. In the early days of the HIV epidemic, vaccine developers took a standard approach in vaccinology, focusing on the wild-type form of the viral surface proteins as the primary immunogens for development. It became clear that the genetic and antigenic variability of HIV, particularly its surface envelope glycoprotein, would preclude this strategy from being a successful one [ 11 ]. A more rational approach toward immunogen design eventually took hold, based on the structural resolution of key epitopes that were the target of potent, broadly neutralizing antibodies, which in many viral pathogen models have been a strong correlate of protection.

In recent years, structural biology and reverse vaccinology have become powerful tools to influence antigen potency. These approaches optimize the immunogenicity of antigens by resolving the structural details of surface proteins as a way to engineer key epitopes as targets of the most potent neutralizing antibodies, particularly those identified after natural infection [ 12 – 14 ]. Much of the focus in rational vaccine design for enveloped viruses, like HIV, has been on stabilizing their surface class I fusion proteins in a prefusion conformation. By honing in on this region, vaccine designers have been able to improve the breadth of neutralization [ 15 ].

One application of this HIV vaccine design strategy was in scaffolding epitopes to elicit antibody responses against the membrane proximal external region of the envelope gp41 subunit [ 16 ]. In this approach, a broadly neutralizing epitope was positioned, in its native conformation, onto a heterologous protein scaffold. This translated into the stabilization of the envelope ectodomain in its trimeric prefusion conformation and the generation of the BG505 SOSIP.664 proteins that contain the targets of broadly neutralizing antibodies [ 17 , 18 ]. The methods of reverse vaccinology have also been used to understand and improve upon modestly successful vaccine strategies—such as that observed in the seminal RV144 trial and its immune correlates analysis, which revealed antibody responses to the gp120 V1/V2 region correlated inversely with infection risk [ 19 ]. While the vaccine candidates used for the prime-boost regimen were not developed by structure-based design, this method is being used by some laboratories for the rational development of subsequent candidates [ 20 – 22 ] as a way to engineer immunogens capable of inducing even more broadly neutralizing antibody repertoires.

Although the methods described above have advanced the science of HIV vaccinology, the greatest leap forward in the use of structural biology for the design of viral surface protein immunogens occurred in the resolution and stabilization of the fusion (F) protein of respiratory syncytial virus (RSV), a major cause of pneumonia in children and the elderly [ 23 – 27 ]. The work with RSV, though owing some of its success to technologies developed through investigations into HIV immunology, has created gains that have reciprocally informed efforts in HIV vaccine research as well as coronavirus vaccine development. Most notably, the evolution of the science culminated in early 2020, with the structural resolution of the SARS-CoV-2 prefusion Spike glycoprotein and its rapid translation into the key immunogen used in the most effective COVID-19 vaccines [ 28 ]. The advances made in structural biology and reverse vaccinology for HIV, RSV, and SARS-CoV-2 are now expanding to vaccine designs for other pathogens, like influenza and meningococcus, and are precipitating a paradigm shift in the entire field of vaccine development.

In the case of genetic vaccines, the platform and the antigen are the primary components. For many licensed vaccines, particularly recombinant proteins, however, there is another important variable that is key to influencing vaccine-elicited immunity: the adjuvant. Both failures and successes in HIV vaccine development have paved the way for the design and discovery of more potent adjuvants. One of the key lessons learned has been that aluminum hydroxide is a poor adjuvant for HIV-1 antigens in humans [ 29 – 33 ]. Unfortunately, MF59 and saponin-based adjuvants have not provided additional benefit in conferring protective efficacy [ 34 – 38 ]. However, new formulations have been developed in hopes of improving the magnitude and the quality of both the antibody- and cell-mediated immune responses [ 39 ]. Furthermore, newer saponin formulations have been shown to induce durable and balanced response profiles [ 40 ]. Despite the substandard performance with HIV vaccines, aluminum adjuvants were still tested in combination with SARS-CoV-2 vaccines such as the inactivated virus vaccines, BBIBP-CorV, and CoronaVac, which provided near 100% protection against severe COVID-19 disease but significantly lower efficacy against infection.

Some of the greatest advances in adjuvant science have come out of investments into liposomal formulations that have been used in concert with antigens across a range of pathogens. Liposomal adjuvants are now being used for two COVID-19 vaccines, including Matrix-M for the Novavax vaccine candidate and ALFQ for the Army’s Spike ferritin nanoparticle (SpFN) vaccine candidate, both of which contain monophosphoryl lipid A (MPLA) and the saponin QS-21 [ 41 – 44 ]. ALFQ now has been in three phase I clinical trials and a third that is likely to begin at the end of 2021 with HIV-1 A244 antigen [ 45 ]. The science of adjuvant design and development across the field of vaccinology will likely be guided by the outcomes of these and other next-generation SARS-CoV-2 recombinant protein vaccines as more data on their efficacy and durability become available.

Prime-Boost Strategies

The immunization schedule and the potential use of different vaccine platforms in that schedule have the potential to strongly influence immunologic memory to a particular antigen. These so-called prime-boost strategies have been evaluated for several decades through modifications of the type, delivery, and timing of immunogens administered as a means toward enhancing both the strength and diversity of the humoral and cell-mediated immune responses. Heterologous prime-boost regimens, though investigated in the early years of the HIV epidemic, had lost momentum as a viable strategy until 2009 when the positive results of the RV144 trial were reported. To date, this is the only trial that demonstrated statistically significant efficacy in preventing HIV acquisition, with a point estimate of 31% at 3.5 years [ 46 ] and 60% at 12 months post-immunization in a subsequent post hoc analysis. This trial was designed to prime with ALVAC-HIV, a canarypox vector, followed by a boost with AIDSVAX B/E, a bivalent subtype C gp120 protein, adjuvanted with aluminum hydroxide gel. Subsequent research has been done to identify the mechanism of protection conferred by this vaccine regimen. Immune correlates analyses revealed that those who were protected had enhanced complement deposition, high levels of IgG1 and IgG3 that targeted the variable loop regions 1 and 2 of gp120, lower IgA levels, and overall more polyfunctional immune response [ 19 ]. Unexpectedly, the concentration of neutralizing antibodies did not correlate with protection [ 47 ]. Other heterologous prime-boost regimens have revealed that a constellation of responses from the innate, adaptive, and cellular arms can be elicited. For instance, DNA platforms and viral vectors tend to elicit stronger T cell responses, whereas protein subunit antigens often provide a stronger humoral response. These prime-boost strategies appeared to add an important dimension to the multifaceted approach of potentiating a more effective response that was being achieved with modifications to antigens, adjuvants, or delivery platforms alone.

Despite early signs of modest efficacy in the RV144 trial, immunogenicity appeared to wane over time. As such, follow-on studies assessed the impact of late boosts with either ALVAC-HIV or AIDSVAX B/E®. ALVAC-HIV alone, however, did not induce significant HIV antibody responses, whereas participants who received ALVAC-HIV and AIDSVAX B/E® or AIDSVAX B/E® alone had antibody levels significantly higher than the peak levels seen in RV144 [ 48 – 51 ]. The latter boosting regimens, even when occurring 6–8 years later, promoted the expansion of lineages of broadly neutralizing antibodies through HCDR3 regions and greater somatic hypermutation.

Among the vaccines that have achieved emergency use authorization in the USA, to date, mRNA-1273 and BNT162b2 use homologous prime-boost regimens while Ad26 .COV2.S is a single vaccine dose as the primary regimen. A subsequent set of “mix and match” studies that boosted individuals with a vaccine different from the original prime have shown a significant potentiation of both the cellular and humoral immune responses as compared to a homologous boost [ 52 ]. Longer-term evaluation will be needed to understand the relative durability and breadth of responses to differing vaccines. Lessons from the field of HIV vaccine development have demonstrated that heterologous prime-boost regimens generate a functional cell-mediated and humoral response. HIV research has demonstrated that combining viral vector or DNA vaccines with protein boosts show the most robust immune profiles.

Immunologic Endpoints

Assessment of vaccine potency, in the course of the development pipeline, is reliant upon standardized assays to assess immunologic responses. The earliest virus neutralization assays that used peripheral blood mononuclear cells (PBMC) and uncloned viruses were often cumbersome, expensive, and difficult to harmonize across laboratories [ 53 ]. To address these limitations, assays with pseudotyped viruses were developed to evaluate antibody-mediated neutralization [ 54 ]. These same platforms were then repurposed for multiple viral pathogens, most recently for SARS-CoV-2.[ 55 – 57 ]. The use of pseudovirus assays has provided the additional benefit for viruses that require higher level biosafety level (BSL) containment, as these pseudoviruses only require BSL-2 conditions, which are more easily maintained in resource-limited settings [ 57 ].

Identification and harmonization of the appropriate immunologic endpoint assays are key to down-selecting and vetting promising vaccine candidates throughout the development pipeline. Advanced-phase clinical trials, however, are often necessary to determine protective efficacy of these vaccines. Ideally, protection or recovery from each infectious disease would correlate with a specific immunologic parameter that would inform the viability of vaccine candidates early in the evaluation process. These have been identified for multiple licensed vaccines in the past, serving as guidelines for the licensing of new vaccines. HIV research has demonstrated, however, that the elucidation of correlates of immunity can be difficult, particularly in the context of an infectious disease that is rarely cleared or cured. As stated earlier, some correlates of protection were identified in the RV144 for trial but, otherwise, markers of protective immunity have eluded HIV researchers [ 58 ]. However, the HIV field has paved a path by which correlates of immunity can be interrogated for other pathogens. A recent study, led in part by HIV researchers, demonstrated that threshold concentrations of neutralizing antibodies against SARS-CoV-2 correlated closely with protective efficacy for major COVID-19 vaccines [ 59 , 60 ]. Identifying correlates of immunity will be important for next-generation COVID-19 vaccines, as these endpoints can reduce the need for large-scale efficacy trials and facilitate the rapid approval, licensure, and bridging of SARS-CoV-2 vaccines, particularly with continued emergence of SARS-CoV-2 variants.

The greatest obstacle to the development of an effective HIV vaccine has been the virus’s high mutation rate and resultant immune evasion. SARS-CoV-2, in contrast, has a much lower mutation rate, thus restricting its genotypic and consequent phenotypic diversity [ 61 ]. In spite of its more limited variability, SARS-CoV-2 variants have been emerging, with significant impact on vaccine efficacy and other public health measures enacted to control the pandemic. The emergence of the Alpha, Beta, Delta, and Omicron variants has raised concerns about the effectiveness of vaccines based on the wild-type strain. Authorized or approved vaccines have had varying success against these variants. Despite the continued, though diminished effectiveness of these vaccines in preventing severe disease or death, continued development of second-generation vaccines is ongoing to prepare for the real threat of more variants, as evidenced by the recent emergence of the B.1.1.529/Omicron [ 62 ] strain. The emergence of this most recent and other viral variants of concern (i.e., Beta) highlights another link between the two topical viruses of this review, as SARS-CoV-2 infection may be prolonged in individuals living with HIV, who inherently have compromised immunity, thus providing favorable conditions for the evolution of more transmissible and antibody-resistant virus variants.

One approach that may offer an advantage in getting ahead of the emergence of new strains and species of coronaviruses is to develop multivalent vaccines that present an array of antigens in a single vaccine formulation so as to elicit a broadly protective response. Several groups are advancing nanoparticle platforms as the basis for this strategy. One in particular, developed by our group, is the SpFN vaccine adjuvanted with ALFQ, which is currently being evaluated in a clinical trial. The continued emergence of new strains and species of coronaviruses necessitates the advancement of these next-generation vaccine strategies that build on the innovation of HIV vaccine science. One of the key lessons from the HIV field is to take a holistic approach toward the generation and testing of new products, one that integrates the disciplines within the scientific community but also engages the participation of society at large.

Community Engagement

Success in containing the SARS-CoV-2 pandemic will rely, at least in part, on the availability, access, and uptake of vaccines. Buy-in on this and other public health measures across communities worldwide will be critical toward this end. Gains in grassroots advocacy and community empowerment made over the course of the HIV/AIDS pandemic provides poignant lessons and guidance for the current pandemic on how best to reach and recruit diverse groups, but particularly marginalized populations. Mirroring the HIV pandemic, COVID-19 has exacerbated health disparities in minority and underserved populations. In the USA, African American and Latinx communities have suffered a disproportionately higher rate of infections and adverse outcomes from COVID-19 [ 63 – 65 ]. Unsurprisingly, vaccine hesitancy, augmented by a long history of mistrust in public health institutions that has been amplified by misinformation, continues to be a barrier to vaccine uptake [ 66 ]. On a global scale, both the HIV/AIDS and COVID-19 pandemics have been complicated by international politics and the concern for equitable distribution of medical countermeasures [ 67 ]. Public health leaders recently have sought to apply the path of international health diplomacy navigated during the height of AIDS pandemic by referencing and adapting the AIDS Vaccine Advocacy Coalition (AVAC) Good Participatory Practice (GPP) guidelines to COVID-19 [ 68 ]. Lessons from AVAC’s guidance documents highlight how an emerging virus could expose and exacerbate inequities in health outcomes [ 69 ]. Building on these lessons, researchers, public health practitioners, and community advocates quickly established the Community Engagement Alliance (CEAL) team and the COVID-19 Prevention Network (CoVPN) Community Engagement Working Group [ 70 , 71 ]. Additionally, the G7 nations committed support early on for global vaccine procurement through the COVID-19 Vaccines Global Access (COVAX) initiative as means to ensure adequate supply vaccines to low- and middle-income countries (LMIC) [ 67 , 72 ]. The initiative has fallen short of its goal so far and has not facilitated the widespread access to life-saving vaccines and treatments in the same way that the most successful HIV campaigns have provided, including the President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. A similar President’s Emergency Plan for Vaccine Access and Relief or “PEPVAR,” as coined in the media, would promote participation of well-resourced countries in favor of international partnerships for development and distribution of medical countermeasures [ 73 ].

The hard lessons from HIV were initially slow to realize and took significant effort to garner political and public support. With time, however, community engagement and advocacy proved to be essential in identifying and addressing systemic inequities that were hindering progress in the control of the HIV/AIDS pandemic: the same is being learned and applied in the current pandemic.

The COVID-19 pandemic has galvanized a vast and deep network of scientific expertise that owes much of its foundation to the advancements made in the fight against HIV. Prescient investments and prioritization of public health programs throughout the HIV pandemic have created a global enterprise that has been leveraged for the current campaign to control the COVID-19 pandemic. Despite the advantages gained from decades of prior groundwork, the public health response to SARS-CoV-2 has revealed gaps in preparedness. The key lessons learned from the current pandemic (Table ​ (Table1), 1 ), just as they did for HIV, will inform policies on how to better prepare for future public health threats.

Key advancements made in HIV vaccine research applied to COVID-19 vaccines

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K. Modjarrad is a principal inventor of the SARS-CoV-2 Spike ferritin nanoparticle (SpFN) vaccine.

This article does not contain any studies with human or animal subjects performed by any of the authors.

Department of Defense.

The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense, or the Henry Jackson Foundation.

This article is part of the Topical Collection on The Global Epidemic

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PACHA Members Discuss HIV Research Highlights from CROI 2024 By HIV.gov

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Each year, the Conference on Retroviruses and Opportunistic Infections (CROI) features an array of exciting new developments in HIV research that can help support the health and well-being of people across the globe. Before the start of the 80 th full council meeting of the Presidential Advisory Council on HIV/AIDS (PACHA) in Houston, TX, HIV.gov had the opportunity to speak with PACHA members Patrick Sullivan, DrPH, MPH, Professor of Epidemiology at Emory University’s Rollins School of Public Health, and Jeff Taylor, Executive Director of the HIV and Aging Research Project, who both attended CROI 2024, about what they presented and what stood out to them at this year’s conference. Watch their conversation Exit Disclaimer :

Mentorship and HIV and Aging Research

Mr. Taylor noted that this year was the first time a formal mentorship program for advocates was launched at the conference, with seasoned mentors paired with new Community Educator Scholars to support and engage them to ensure they got the most out of CROI. He also reflected on the range of research presented at CROI related to HIV and aging. He noted that there continue to be findings presented via abstracts and presentations from the NIH-supported  REPRIEVE trial , a global study that demonstrated that a statin, a cholesterol-lowering medication, may offset the high risk of cardiovascular disease in people with HIV by more than a third, potentially preventing one in five major cardiovascular events (e.g., heart attacks, strokes, or surgery to open a blocked artery) or premature deaths in this population. As he noted,  new clinical guidelines were recently published based on those findings, helping clinicians better support the health of those ages 40-75. ( View HIV.gov’s CROI 2024 conversation with Dr. Carl Dieffenbach about new REPRIEVE trial findings .)

The Further Promise of PrEP

Dr. Sullivan discussed new evidence from a study he and his colleagues at Emory University conducted Exit Disclaimer showing that, over the past decade, U.S. states with high PrEP coverage among those who need it experienced steeper declines in new HIV diagnoses rates than states with low PrEP coverage. Their analysis showed that from 2012 to 2021, states with the lowest levels of PrEP coverage saw an annual increase in new HIV diagnoses, while all other states saw an annual decrease in HIV diagnoses, with the largest decreases among states with the highest levels of PrEP coverage. In other words, he emphasized, while we’ve known for decades that PrEP works to prevent HIV at the individual level, we now know that when we remove barriers to PrEP access and take PrEP to scale, we can see an impact on the population level as well. He further noted that other studies presented at CROI 2024 about all stages in the PrEP cascade—awareness, access, uptake, and adherence—show that we have the tools to get us to that high level of PrEP coverage and better knowledge of how to deploy them.

Catch Up on Other CROI HIV Research Updates

Mr. Taylor also shared an important observation about the opening session with the HIV.gov team as we were working on this blog. He noted, “There was ongoing discussion at CROI regarding stigma as an obstacle to ending the epidemic. Ugandan activist Frank Mugisha, Sexual Minorities Uganda (SMUG), highlighted the chilling impact of new laws criminalizing LGBTQ individuals during the conference's opening plenary. He added that these laws hinder access to HIV care and threaten progress against HIV and that discriminatory policies can cripple the fight against HIV.”

HIV.gov has shared other interviews from CROI 2024 with federal HIV leaders, participating researchers, and community members. You can find all of them on HIV.gov’s social media channels and with recaps here on the blog available by using the CROI topic tag .

More than 3,600 HIV and infectious disease researchers from 73 countries gathered in Denver and virtually from March 3-6 this year for CROI, an annual scientific meeting on the latest research that can help accelerate global progress in the response to HIV and other infectious diseases, including STIs and viral hepatitis. Over 1,000 summaries of original research were presented. Visit the conference website Exit Disclaimer for more information. Session webcasts and more information will be published there for public access in 30 days.

Related HIV.gov Blogs

• Aging Aging and HIV
• CROI Conference on Retroviruses & Opportunistic Infections
• PACHA Presidential Advisory Council on HIV/AIDS
• PrEP Pre-Exposure Prophylaxis