Current Status of HIV-1 Vaccines

Anna Hargrave 1, Abu Salim Mustafa 2, Asma Hanif 3, Javed H Tunio 4, Shumaila Nida M Hanif 1


 

Affiliations

16 September 2021

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doi: DOI: 10.3390/vaccines9091026

Abstract

HIV-1 infection and its progression to AIDS remains a significant global health challenge, particularly for low-income countries. Developing a vaccine to prevent HIV-1 infections has proven to be immensely challenging with complex biological acquisition and infection, unforeseen clinical trial disappointments, and funding issues. This paper discusses important landmarks of progress in HIV-1 vaccine development, various vaccine strategies, and clinical trials.

Keywords: HIV; clinical phases; vaccines.

Conflict of interest statement

The authors declare no conflict of interest.

References

  1.  
    1. UNAIDS Global HIV & AIDS Statistics. [(accessed on 14 July 2021)]. Available online: https://www.unaids.org/en/resources/fact-sheet.
  2.  
    1. Rezaei T., Khalili S., Baradaran B., Mosafer J., Rezaei S., Mokhtarzadeh A., de la Guardia M. Recent advances on HIV DNA vaccines development: Stepwise improvements to clinical trials. J. Control. Release. 2019;316:116–137. doi: 10.1016/j.jconrel.2019.10.045. - DOI - PubMed
  3.  
    1. Fauci A.S., Lane H.C. Four decades of HIV/AIDS—Much accomplished, much to do. N. Engl. J. Med. 2020;383:1–4. doi: 10.1056/NEJMp1916753. - DOI - PubMed
  4.  
    1. Wang H.-B., Mo Q.-H., Yang Z. HIV Vaccine Research: The Challenge and the Way Forward. J. Immunol. Res. 2015;2015:503978. doi: 10.1155/2015/503978. - DOI - PMC - PubMed
  5.  
    1. Hsu D.C., O’Connell R.J. Progress in HIV vaccine development. Hum. Vaccines Immunother. 2017;13:1018–1030. doi: 10.1080/21645515.2016.1276138. - DOI - PMC - PubMed
  6.  
    1. Ng’Uni T., Chasara C., Ndhlovu Z.M. Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions. Front. Immunol. 2020;11:590780. doi: 10.3389/fimmu.2020.590780. - DOI - PMC - PubMed
  7.  
    1. Esparza J. A brief history of the global effort to develop a preventive HIV vaccine. Vaccine. 2013;31:3502–3518. doi: 10.1016/j.vaccine.2013.05.018. - DOI - PubMed
  8.  
    1. Hanke T. Aiming for protective T-cell responses: A focus on the first generation conserved-region HIVconsv vaccines in preventive and therapeutic clinical trials. Expert Rev. Vaccines. 2019;18:1029–1041. doi: 10.1080/14760584.2019.1675518. - DOI - PubMed
  9.  
    1. Collins D.R., Gaiha G.D., Walker B.D. CD8+ T cells in HIV control, cure and prevention. Nat. Rev. Immunol. 2020;20:471–482. doi: 10.1038/s41577-020-0274-9. - DOI - PMC - PubMed
  10.  
    1. Stephenson K., Barouch D.H. A global approach to HIV -1 vaccine development. Immunol. Rev. 2013;254:295–304. doi: 10.1111/imr.12073. - DOI - PMC - PubMed
  11.  
    1. Bekker L.-G., Tatoud R., Dabis F., Feinberg M., Kaleebu P., Marovich M., Ndung’U T., Russell N., Johnson J., Luba M., et al. The complex challenges of HIV vaccine development require renewed and expanded global commitment. Lancet. 2020;395:384–388. doi: 10.1016/S0140-6736(19)32682-0. - DOI - PubMed
  12.  
    1. Esparza J. A New Scientific Paradigm may be Needed to Finally Develop an HIV Vaccine. Front. Immunol. 2015;6:124. doi: 10.3389/fimmu.2015.00124. - DOI - PMC - PubMed
  13.  
    1. Ross A.L., Bråve A., Scarlatti G., Manrique A., Buonaguro L. Progress towards development of an HIV vaccine: Report of the AIDS Vaccine 2009 Conference. Lancet Infect. Dis. 2010;10:305–316. doi: 10.1016/S1473-3099(10)70069-4. - DOI - PubMed
  14.  
    1. Gray G.E., Laher F., Lazarus E., Ensoli B., Corey L. Approaches to preventative and therapeutic HIV vaccines. Curr. Opin. Virol. 2016;17:104–109. doi: 10.1016/j.coviro.2016.02.010. - DOI - PMC - PubMed
  15.  
    1. Gray G., Buchbinder S., Duerr A. Overview of STEP and Phambili trial results: Two phase IIb test-of-concept studies investigating the efficacy of MRK adenovirus type 5 gag/pol/nef subtype B HIV vaccine. Curr. Opin. HIV AIDS. 2010;5:357–361. doi: 10.1097/COH.0b013e32833d2d2b. - DOI - PMC - PubMed
  16.  
    1. Lu S. Heterologous prime-boost vaccination. Curr. Opin. Virol. 2009;21:346–351. doi: 10.1016/j.coi.2009.05.016. - DOI - PMC - PubMed
  17.  
    1. Excler J.-L., Kim J.H. Novel prime-boost vaccine strategies against HIV-1. Expert Rev. Vaccines. 2019;18:765–779. doi: 10.1080/14760584.2019.1640117. - DOI - PubMed
  18.  
    1. Mayr A., Hochstein-Mintzel V., Stickl H. Abstammung, Eigenschaften und Verwendung des attenuierten Vaccinia-Stammes MVA. Infection. 1975;105:6–14. doi: 10.1007/BF01641272. - DOI
  19.  
    1. Zolla-Pazner S., Michael N.L., Kim J.H. A tale of four studies: HIV vaccine immunogenicity and efficacy in clinical trials. Lancet HIV. 2021;8:e449–e452. doi: 10.1016/S2352-3018(21)00073-4. - DOI - PMC - PubMed
  20.  
    1. Haynes B.F., Gilbert P.B., McElrath M.J., Zolla-Pazner S., Tomaras G.D., Alam S.M., Evans D.T., Montefiori D.C., Karnasuta C., Sutthent R., et al. Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial. N. Engl. J. Med. 2012;366:1275–1286. doi: 10.1056/NEJMoa1113425. - DOI - PMC - PubMed
  21.  
    1. Mu Z., Haynes B., Cain D. HIV mRNA Vaccines—Progress and Future Paths. Vaccines. 2021;9:134. doi: 10.3390/vaccines9020134. - DOI - PMC - PubMed
  22.  
    1. Scheid J.F., Mouquet H., Ueberheide B., Diskin R., Klein F., Oliveira T.Y.K., Pietzsch J., Fenyo D., Abadir A., Velinzon K., et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science. 2011;333:1633–1637. doi: 10.1126/science.1207227. - DOI - PMC - PubMed
  23.  
    1. Caskey M., Klein F., Lorenzi J.C.C., Seaman M.S., West A.P., Jr., Buckley N., Kremer G., Nogueira L., Braunschweig M., Scheid J.F., et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature. 2015;522:487–491. doi: 10.1038/nature14411. - DOI - PMC - PubMed
  24.  
    1. Lynch R.M., Boritz E., Coates E.E., DeZure A., Madden P., Costner P., Enama M.E., Plummer S., Holman L., Hendel C.S., et al. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci. Transl. Med. 2015;7:319ra206. doi: 10.1126/scitranslmed.aad5752. - DOI - PubMed
  25.  
    1. Corey L., Gilbert P.B., Juraska M., Montefiori D.C., Morris L., Karuna S.T., Edupuganti S., Mgodi N.M., Decamp A.C., Rudnicki E., et al. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. N. Engl. J. Med. 2021;384:1003–1014. doi: 10.1056/NEJMoa2031738. - DOI - PMC - PubMed
  26.  
    1. Priddy F.H., Lewis D.J.M., Gelderblom H.C., Hassanin H., Streatfield C., LaBranche C., Hare J., Cox J., Dally L., Bendel D., et al. Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: A phase 1 randomised controlled trial. Lancet HIV. 2019;6:e230–e239. doi: 10.1016/S2352-3018(19)30003-7. - DOI - PMC - PubMed
  27.  
    1. Palesch D., Kirchhoff F. First Steps toward a Globally Effective HIV/AIDS Vaccine. Cell. 2013;155:495–497. doi: 10.1016/j.cell.2013.10.012. - DOI - PubMed
  28.  
    1. Barouch D.H., Tomaka F.L., Wegmann F., Stieh D.J., Alter G., Robb M.L., Michael N.L., Peter L., Nkolola J.P., Borducchi E.N., et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19) Lancet. 2018;392:232–243. doi: 10.1016/S0140-6736(18)31364-3. - DOI - PMC - PubMed
  29.  
    1. Fred Hutchinson Cancer Research Center Experimental Phase 2b HIV Vaccine Regimen Provides Insufficient Protection in Preventing HIV. [(accessed on 9 September 2021)]. Available online: https://www.newswise.com/articles/experimental-phase-2b-hiv-vaccine-regi....
  30.  
    1. Sadoff J., Gray G., Vandebosch A., Cárdenas V., Shukarev G., Grinsztejn B., Goepfert P.A., Truyers C., Fennema H., Spiessens B., et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. N. Engl. J. Med. 2021;384:2187–2201. doi: 10.1056/NEJMoa2101544. - DOI - PMC - PubMed
  31.  
    1. A Study to Assess Safety and Immunogenicity of Conserved Mosaic HIV-1 Vaccines. [(accessed on 16 July 2021)]; Available online: https://clinicaltrials.gov/ct2/show/NCT04586673.
  32.  
    1. Jones L.D., Moody M.A., Thompson A.B. Innovations in HIV-1 Vaccine Design. Clin. Ther. 2020;42:499–514. doi: 10.1016/j.clinthera.2020.01.009. - DOI - PMC - PubMed
  33.  
    1. Polack F.P., Thomas S.J., Kitchin N., Absalon J., Gurtman A., Lockhart S., Perez J.L., Marc G.P., Moreira E.D., Zerbini C., et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N. Engl. J. Med. 2020;383:2603–2615. doi: 10.1056/NEJMoa2034577. - DOI - PMC - PubMed
  34.  
    1. Baden L.R., El Sahly H.M., Essink B., Kotloff K., Frey S., Novak R., Diemert D., Spector S.A., Rouphael N., Creech C.B., et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021;384:403–416. doi: 10.1056/NEJMoa2035389. - DOI - PMC - PubMed
  35.  
    1. Venkatesan P. Preliminary phase 1 results from an HIV vaccine candidate trial. Lancet Microbe. 2021;2:e95. doi: 10.1016/S2666-5247(21)00042-2. - DOI
  36.  
    1. A Phase 1 Study to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core) [(accessed on 10 September 2021)]; Available online: https://clinicaltrials.gov/ct2/show/NCT05001373.
  37.  
    1. Eisinger R.W., Lerner A.M., Fauci A.S. HIV/AIDS in the era of COVID-19: A juxtaposition of two pandemics. J. Infect. Dis. 2021:jiab114. doi: 10.1093/infdis/jiab114. - DOI - PMC - PubMed
  38.  
    1. Haynes B.F. SARS-CoV-2 and HIV-1—A tale of two vaccines. Nat. Rev. Immunol. 2021;21:543–544. doi: 10.1038/s41577-021-00589-w. - DOI - PMC - PubMed

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