Updated Studies on the Development of HIV Therapeutic Vaccine

Author(s): Mona Sadat Larijani, Amitis Ramezani, Seyed Mehdi Sadat*.

Journal Name: Current HIV Research

Volume 17 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Among the various types of pharmaceuticals, vaccines have a special place. However, in the case of HIV, nearly after 40 years of its discovery, an effective vaccine still is not available. The reason lies in several facts mainly the variability and smartness of HIV as well as the complexity of the interaction between HIV and immune responses. A robust, effective, and longterm immunity is undoubtedly what a successful preventive vaccine should induce in order to prevent the infection of HIV. Failure of human trials to this end has led to the idea of developing therapeutic vaccines with the purpose of curing already infected patients by boosting their immune responses against the virus. Nevertheless, the exceptional ability of the virus to escape the immune system based on the genetically diverse envelope and variable protein products have made it difficult to achieve an efficient therapeutic vaccine.

Objective: We aimed at studying and comparing different approaches to HIV therapeutic vaccines.

Methods: In this review, we summarized the human trials undergoing on HIV therapeutic vaccination which are registered in the U.S. clinical trial database (clinicaltrials.gov). These attempts are divided into different tables, according to the type of formulation and application in order to classify and compare their results.

Result/Conclusion: Among several methods applied in studied clinical trials which are mainly divided into DNA, Protein, Peptide, Viral vectors, and Dendritic cell-based vaccines, protein vaccine strategy is based on Tat protein-induced anti-Tat Abs in 79% HIV patients. However, the studies need to be continued to achieve a durable efficient immune response against HIV-1.

Keywords: HIV, vaccine, therapeutic, clinical trials, accessing antiretroviral therapy (ART), dendritic cell.

[1]
HIV/AIDS fact sheet: World Health Organization 2017.
[2]
Sidibé M. UNAIDS DATA 2017 Joint United Nations Programme on HIV/AIDS. UNAIDS 2017.
[3]
Barry SM, Mena Lora AJ, Novak RM. Trial, error, and breakthrough: A review of HIV vaccine development. J AIDS Clin Res 2014; 05(11): 359.
[4]
Barré-Sinoussi F, Ross AL, Delfraissy J-F. Past, present and future: 30 years of HIV research. Nat Rev Microbiol 2013; 11(12): 877-83.
[http://dx.doi.org/10.1038/nrmicro3132] [PMID: 24162027]
[5]
Sekaly RP. The failed HIV Merck vaccine study: A step back or a launching point for future vaccine development? J Exp Med 2008; 205(1): 7-12.
[http://dx.doi.org/10.1084/jem.20072681] [PMID: 18195078]
[6]
Kim JH, Excler JL, Michael NL. Lessons from the RV144 Thai phase III HIV-1 vaccine trial and the search for correlates of protection. Annu Rev Med 2015; 66: 423-37.
[http://dx.doi.org/10.1146/annurev-med-052912-123749] [PMID: 25341006]
[7]
Koff WC. A shot at AIDS. Curr Opin Biotechnol 2016; 42: 147-51.
[http://dx.doi.org/10.1016/j.copbio.2016.03.007] [PMID: 27153215]
[8]
Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. MOPH-TAVEG Investigators. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009; 361(23): 2209-20.
[http://dx.doi.org/10.1056/NEJMoa0908492] [PMID: 19843557]
[9]
ClinicalTrials.gov. 2019.https://clinicaltrials.gov/ct2/home
[10]
Hammer SM, Sobieszczyk ME, Janes H, et al. HVTN 505 Study Team. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med 2013; 369(22): 2083-92.
[http://dx.doi.org/10.1056/NEJMoa1310566] [PMID: 24099601]
[11]
Karasavvas N, Billings E, Rao M, et al. MOPH TAVEG Collaboration. The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120. AIDS Res Hum Retroviruses 2012; 28(11): 1444-57.
[http://dx.doi.org/10.1089/aid.2012.0103] [PMID: 23035746]
[12]
Sekaly R-P. The failed HIV Merck vaccine study: A step back or a launching point for future vaccine development? J Exp Med 2008; 205(1): 7-12.
[http://dx.doi.org/10.1084/jem.20072681] [PMID: 18195078]
[13]
Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF. rgp120 HIV Vaccine Study Group. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 2005; 191(5): 654-65.
[http://dx.doi.org/10.1086/428404] [PMID: 15688278]
[14]
Suntharasamai P, Martin M, Vanichseni S, et al. Bangkok Vaccine Evaluation Group. Factors associated with incarceration and incident Human Immunodeficiency Virus (HIV) infection among injection drug users participating in an HIV vaccine trial in Bangkok, Thailand, 1999-2003. Addiction 2009; 104(2): 235-42.
[http://dx.doi.org/10.1111/j.1360-0443.2008.02436.x] [PMID: 19149819]
[15]
Sosa D, Jayant RD, Kaushik A, Nair M. Current status of human immunodeficiency virus vaccines. Vaccin Res Open J 2016; 1(1): e3-5.
[http://dx.doi.org/10.17140/VROJ-1-e002]
[16]
Robinson HL. HIV/AIDS Vaccines: 2018. Clin Pharmacol Ther 2018; 104(6): 1062-73.
[http://dx.doi.org/10.1002/cpt.1208] [PMID: 30099743]
[17]
Deeks SG, Overbaugh J, Phillips A, Buchbinder S. HIV infection. Nat Rev Dis Primers 2015; 1: 15035.
[http://dx.doi.org/10.1038/nrdp.2015.35] [PMID: 27188527]
[18]
Demers KR, Reuter MA, Betts MR. CD8(+) T-cell effector function and transcriptional regulation during HIV pathogenesis. Immunol Rev 2013; 254(1): 190-206.
[http://dx.doi.org/10.1111/imr.12069] [PMID: 23772621]
[19]
Ayyavoo DGaV. Innate immune evasion strategies by human immunodeficiency virus type 1. Hindawi Publishing Corporation 2013; pp. 1-10.
[20]
Corey L, Gilbert PB, Tomaras GD, Haynes BF, Pantaleo G, Fauci AS. Immune correlates of vaccine protection against HIV-1 acquisition. Sci Transl Med 2015; 7(310)310rv7
[http://dx.doi.org/10.1126/scitranslmed.aac7732] [PMID: 26491081]
[21]
Rappuoli R, Aderem A. A 2020 vision for vaccines against HIV, tuberculosis and malaria. Nature 2011; 473(7348): 463-9.
[http://dx.doi.org/10.1038/nature10124] [PMID: 21614073]
[22]
Al-Jabri AA. Mechanisms of host resistance against HIV infection and progression to AIDS. Sultan Qaboos Univ Med J 2007; 7(2): 82-96.
[PMID: 21748089]
[23]
Dashti A, DeVico AL, Lewis GK, Sajadi MM. Broadly neutralizing antibodies against HIV: Back to blood. Trends Mol Med 2019; 25(3): 228-40.
[http://dx.doi.org/10.1016/j.molmed.2019.01.007] [PMID: 30792120]
[24]
Haberer JE, Baeten JM, Campbell J, et al. Adherence to antiretroviral prophylaxis for HIV prevention: A substudy cohort within a clinical trial of serodiscordant couples in East Africa. PLoS Med 2013; 10(9)e1001511
[http://dx.doi.org/10.1371/journal.pmed.1001511] [PMID: 24058300]
[25]
Sela M, Hilleman MR. Therapeutic vaccines: Realities of today and hopes for tomorrow. Proceedings of the National Academy of Sciences of the United States of America.
[http://dx.doi.org/10.1073/pnas.0405924101]
[26]
Gulley JL. Therapeutic vaccines: The ultimate personalized therapy? Hum Vaccin Immunother 2013; 9(1): 219-21.
[http://dx.doi.org/10.4161/HV.22106] [PMID: 22995839]
[27]
U.S. National Library of Medicine. 2018.https://www. clinicaltrials.gov
[28]
Felber BK, Valentin A, Rosati M, Bergamaschi C, Pavlakis GN. HIV DNA vaccine: Stepwise improvements make a difference. Vaccines (Basel) 2014; 2(2): 354-79.
[http://dx.doi.org/10.3390/vaccines2020354] [PMID: 26344623]
[29]
Chupradit K, Moonmuang S, Nangola S, et al. Current peptide and protein candidates challenging HIV therapy beyond the vaccine era. Viruses 2017; 9(10): 281.
[http://dx.doi.org/10.3390/v9100281] [PMID: 28961190]
[30]
Saxena M, Bhardwaj N. Re-emergence of dendritic cell vaccines for cancer treatment. Trends Cancer 2018; 4(2): 119-37.
[http://dx.doi.org/10.1016/j.trecan.2017.12.007] [PMID: 29458962]
[31]
Sabado RL, Bhardwaj N. Cancer immunotherapy: Dendritic-cell vaccines on the move. Nature 2015; 519(7543): 300-1.
[http://dx.doi.org/10.1038/nature14211] [PMID: 25762139]
[32]
Macatangay BJC, Riddler SA, Wheeler ND, et al. Therapeutic vaccination with dendritic cells loaded with autologous HIV type 1-infected apoptotic cells. J Infect Dis 2016; 213(9): 1400-9.
[http://dx.doi.org/10.1093/infdis/jiv582] [PMID: 26647281]
[33]
Rinaldo CR. Dendritic cell-based human immunodeficiency virus vaccine. J Intern Med 2009; 265(1): 138-58.
[http://dx.doi.org/10.1111/j.1365-2796.2008.02047.x] [PMID: 19093966]
[34]
Coelho AVC, de Moura RR, Kamada AJ, et al. Dendritic cell-based immunotherapies to fight HIV: How far from a success story? A systematic review and meta-analysis. Int J Mol Sci 2016; 17(12): 1985.
[http://dx.doi.org/10.3390/ijms17121985] [PMID: 27898045]
[35]
Jacobson JM, Routy JP, Welles S, et al. Dendritic cell immunotherapy for HIV-1 infection using autologous HIV-1 RNA: A randomized, double-blind, placebo-controlled clinical trial. J Acquir Immune Defic Syndr 2016; 72(1): 31-8.
[36]
Macatangay BJ, Riddler SA, Wheeler ND, et al. Therapeutic vaccination with dendritic cells loaded with autologous HIV type 1-infected apoptotic cells. J Infect Dis 2016; 213(9): 1400-9.
[http://dx.doi.org/10.1093/infdis/jiv582] [PMID: 26647281]
[37]
García F, Plana M, Climent N, León A, Gatell JM, Gallart T. Dendritic cell based vaccines for HIV infection: The way ahead. Hum Vaccin Immunother 2013; 9(11): 2445-52.
[http://dx.doi.org/10.4161/hv.25876] [PMID: 23912672]
[38]
García F, Climent N, Guardo AC, et al. DCV2/MANON07-ORVACS study group. A dendritic cell-based vaccine elicits T cell responses associated with control of HIV-1 replication. Sci Transl Med 2013; 5(166)166ra2
[http://dx.doi.org/10.1126/scitranslmed.3004682] [PMID: 23283367]
[39]
Nascimento IP, Leite LCC. Recombinant vaccines and the development of new vaccine strategies. Braz J Med Biol Res 2012; 45(12): 1102-11.
[PMID: 22948379]
[40]
Lema D, Garcia A, De Sanctis JB. HIV vaccines: A brief overview. Scand J Immunol 2014; 80(1): 1-11.
[http://dx.doi.org/10.1111/sji.12184] [PMID: 24813074]
[41]
Kinloch-de Loes S. Loes SK-d. Role of therapeutic vaccines in the control of HIV-1. J Antimicrob Chemother 2004; 53(4): 562-6.
[http://dx.doi.org/10.1093/jac/dkh132] [PMID: 14985273]
[42]
Bayon E, Morlieras J, Dereuddre-Bosquet N, et al. Overcoming immunogenicity issues of HIV p24 antigen by the use of innovative nanostructured lipid carriers as delivery systems: evidences in mice and non-human primates. NPJ Vaccines 2018; 3: 46.
[http://dx.doi.org/10.1038/s41541-018-0086-0]
[43]
Dinges W, Girard PM, Podzamczer D, et al. The F4/AS01B HIV-1 vaccine candidate is safe and immunogenic, but does not show viral efficacy in antiretroviral therapy-naive, HIV-1-infected adults: a randomized controlled trial. Medicine (Baltimore) 2016; 95(6)e2673
[http://dx.doi.org/10.1097/MD.0000000000002673] [PMID: 26871794]
[44]
Ensoli F, Cafaro A, Casabianca A, et al. HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: Results of a randomized phase II exploratory clinical trial. Retrovirology 2015; 12: 33.
[http://dx.doi.org/10.1186/s12977-015-0151-y] [PMID: 25924841]
[45]
Loret EP, Darque A, Jouve E, et al. Intradermal injection of a tat oyi-based therapeutic HIV vaccine reduces of 1.5 log copies/mL the HIV RNA rebound median and no HIV DNA rebound following cART interruption in a phase I/II randomized controlled clinical trial. Retrovirology 2016; 13: 21.
[http://dx.doi.org/10.1186/s12977-016-0251-3] [PMID: 27036656]
[46]
Goldstein G, Damiano E, Donikyan M, Pasha M, Beckwith E, Chicca J. HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation: HIV rebound with current ART appears to be due to infection with new endogenous founder virus and not to resurgence of pre-existing Tat-dependent viremia. Hum Vaccin Immunother 2012; 8(10): 1425-30.
[http://dx.doi.org/10.4161/hv.21616] [PMID: 23095869]
[47]
Larijani MS, Sadat SM, Bolhassani A, Pouriayevali MH, Bahramali G, Ramezani A. in silico design and immunologic evaluation of HIV-1 p24-nef fusion protein to approach a therapeutic vaccine candidate. Curr HIV Res 2018; 16(5): 322-37.
[http://dx.doi.org/10.2174/1570162X17666190102151717] [PMID: 30605062]
[48]
Skwarczynski M, Toth I. Peptide-based synthetic vaccines. Chem Sci (Camb) 2016; 7(2): 842-54.
[http://dx.doi.org/10.1039/C5SC03892H] [PMID: 28791117]
[49]
Rockstroh JK, Asmuth D, Pantaleo G, et al. Re-boost immunizations with the peptide-based therapeutic HIV vaccine, Vacc-4x, restores geometric mean viral load set-point during treatment interruption. PLoS One 2019; 14(1)e0210965
[http://dx.doi.org/10.1371/journal.pone.0210965] [PMID: 30699178]
[50]
Pentier JM, Sewell AK, Miles JJ. Advances in T-cell epitope engineering. Front Immunol 2013; 4: 133.
[http://dx.doi.org/10.3389/fimmu.2013.00133] [PMID: 23761792]
[51]
Liu TY, Hussein WM, Jia Z, et al. Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer. Biomacromolecules 2013; 14(8): 2798-806.
[http://dx.doi.org/10.1021/bm400626w] [PMID: 23837675]
[52]
Pollard RB, Rockstroh JK, Pantaleo G, et al. Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 2014; 14(4): 291-300.
[http://dx.doi.org/10.1016/S1473-3099(13)70343-8] [PMID: 24525316]
[53]
Ho Tsong Fang R, Launay O, Rouzioux C, et al. VAC-3S, a safe immunotherapeutic HIV vaccine decreased total HIV DNA and increased CD4/CD8 ratio: Phase I final results Towards an HIV Cure Symposium; Vancouver 2015.
[54]
Brekke K, Sommerfelt M, Ökvist M, Dyrhol-Riise AM, Kvale D. The therapeutic HIV Env C5/gp41 vaccine candidate Vacc-C5 induces specific T cell regulation in a phase I/II clinical study. BMC Infect Dis 2017; 17(1): 228.
[http://dx.doi.org/10.1186/s12879-017-2316-x] [PMID: 28340570]
[55]
Jensen KJ, Gómez Román VR, Jensen SS, et al. Clade A HIV-1 Gag-specific T cell responses are frequent but do not correlate with viral loads in a cohort of treatment-naive HIV-infected individuals living in Guinea-Bissau. Clin Vaccine Immunol 2012; 19(12): 1999-2001.
[http://dx.doi.org/10.1128/CVI.00399-12] [PMID: 23081817]
[56]
Boffito M, Fox J, Bowman C, et al. Safety, immunogenicity and efficacy assessment of HIV immunotherapy in a multi-centre, double-blind, randomised, Placebo-controlled Phase Ib human trial. Vaccine 2013; 31(48): 5680-6.
[http://dx.doi.org/10.1016/j.vaccine.2013.09.057] [PMID: 24120550]
[57]
Ferraro B, Morrow MP, Hutnick NA, Shin TH, Lucke CE, Weiner DB. Clinical applications of DNA vaccines: current progress. Clin Infect Dis 2011; 53(3): 296-302.
[http://dx.doi.org/10.1093/cid/cir334] [PMID: 21765081]
[58]
Lisziewicz J, Calarota SA, Lori F. The potential of topical DNA vaccines adjuvanted by cytokines. Expert Opin Biol Ther 2007; 7(10): 1563-74.
[http://dx.doi.org/10.1517/14712598.7.10.1563] [PMID: 17916048]
[59]
van Diepen MT, Chapman R, Douglass N, et al. Prime-boost immunizations with DNA, modified vaccinia virus ankara, and protein-based vaccines elicit robust HIV-1 tier 2 neutralizing antibodies against the CAP256 superinfecting virus. J Virol 2019; 93(8): e02155-18.
[http://dx.doi.org/10.1128/JVI.02155-18] [PMID: 30760570]
[60]
Munson P, Liu Y, Bratt D, et al. Therapeutic conserved elements (CE) DNA vaccine induces strong T-cell responses against highly conserved viral sequences during simian-human immunodeficiency virus infection. Hum Vaccin Immunother 2018; 14(7): 1820-31.
[http://dx.doi.org/10.1080/21645515.2018.1448328] [PMID: 29648490]
[61]
Jacobson JM, Zheng L, Wilson CC, et al. The safety and immunogenicity of an interleukin-12-enhanced multiantigen DNA vaccine delivered by electroporation for the treatment of HIV-1 infection. J Acquir Immune Defic Syndr 2016; 71(2): 163-71.
[62]
Tebas P, Ramirez L, Morrow M, et al. Potent cellular immune responses after therapeutic immunization of HIV-positive patients with the PENNVAX®-B DNA vaccine in a Phase I Trial. Retrovirology 2012; 9(2): 276.
[http://dx.doi.org/10.1186/1742-4690-9-S2-P276]
[63]
Shapiro SZ. Lessons for general vaccinology research from attempts to develop an HIV vaccine. Vaccine 2019; 37(26): 3400-8.
[http://dx.doi.org/10.1016/j.vaccine.2019.04.005] [PMID: 30979571]
[64]
Tohidi F, Sadat SM, Bolhassani A, Yaghobi R. Construction and production of HIV-VLP harboring MPER-V3 for potential vaccine study. Curr HIV Res 2017; 15(6): 434-9.
[PMID: 29046160]
[65]
Sadat SM, Zabihollahi R, Aghasadeghi MR, et al. Application of SCR priming VLP boosting as a novel vaccination strategy against HIV-1. Curr HIV Res 2011; 9(3): 140-7.
[http://dx.doi.org/10.2174/157016211795945223] [PMID: 21443517]
[66]
Barouch DH. Novel adenovirus vector-based vaccines for HIV-1. Curr Opin HIV AIDS 2010; 5(5): 386-90.
[http://dx.doi.org/10.1097/COH.0b013e32833cfe4c] [PMID: 20978378]
[67]
Lauer KB, Borrow R, Blanchard TJ. Multivalent and multipathogen viral vector vaccines. Clin Vaccine Immunol 2017; 24(1): e00298-16.
[http://dx.doi.org/10.1128/CVI.00298-16] [PMID: 27535837]
[68]
Alayo QA, Provine NM, Penaloza-MacMaster P. Novel concepts for HIV vaccine vector design. MSphere 2017; 2(6): e00415-7.
[http://dx.doi.org/10.1128/mSphere.00415-17] [PMID: 29242831]
[69]
Provine NM, Larocca RA, Penaloza-MacMaster P, et al. Longitudinal requirement for CD4+ T cell help for adenovirus vector-elicited CD8+ T cell responses. J Immunol 2014; 192(11): 5214-25.
[70]
Ura T, Okuda K, Shimada M. Developments in viral vector-based vaccines. Vaccines (Basel) 2014; 2(3): 624-41.
[http://dx.doi.org/10.3390/vaccines2030624] [PMID: 26344749]
[71]
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006; 124(4): 783-801.
[http://dx.doi.org/10.1016/j.cell.2006.02.015] [PMID: 16497588]
[72]
Hancock G, Morón-López S, Kopycinski J, et al. Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects. J Int AIDS Soc 2017; 20(1): 21171.
[http://dx.doi.org/10.7448/IAS.20.1.21171] [PMID: 28537062]
[73]
Tung FY, Tung JK, Pallikkuth S, Pahwa S, Fischl MA. A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy. Vaccine 2016; 34(19): 2225-32.
[http://dx.doi.org/10.1016/j.vaccine.2016.03.021] [PMID: 27002500]
[74]
Thompson M, Heath SL, Sweeton B, et al. DNA/MVA vaccination of HIV-1 infected participants with viral suppression on antiretroviral therapy, followed by treatment interruption: Elicitation of immune responses without control of re-emergent virus. PLoS One 2016; 11(10)e0163164
[http://dx.doi.org/10.1371/journal.pone.0163164] [PMID: 27711228]
[75]
Persaud D, Luzuriaga K, Ziemniak C, et al. Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir. AIDS 2011; 25(18): 2227-34.
[http://dx.doi.org/10.1097/QAD.0b013e32834cdaba] [PMID: 21918423]
[76]
Gao Y, McKay PF, Mann JFS. advances in HIV-1 vaccine development. Viruses 2018; 10(4): 167.
[http://dx.doi.org/10.3390/v10040167] [PMID: 29614779]
[77]
Klasse PJ, Ketas TJ, Cottrell CA, et al. Epitopes for neutralizing antibodies induced by HIV-1 envelope glycoprotein BG505 SOSIP trimers in rabbits and macaques. PLoS Pathog 2018; 14(2)e1006913
[http://dx.doi.org/10.1371/journal.ppat.1006913] [PMID: 29474444]
[78]
Keele BF, Giorgi EE, Salazar-Gonzalez JF, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci USA 2008; 105(21): 7552-7.
[http://dx.doi.org/10.1073/pnas.0802203105] [PMID: 18490657]
[79]
Trovato M, D’Apice L, Prisco A, De Berardinis P. HIV vaccination: A roadmap among advancements and concerns. Int J Mol Sci 2018; 19(4): 1241.
[http://dx.doi.org/10.3390/ijms19041241] [PMID: 29671786]
[80]
Fauci AS, Marston HD. Ending AIDS--is an HIV vaccine necessary? N Engl J Med 2014; 370(6): 495-8.
[http://dx.doi.org/10.1056/NEJMp1313771] [PMID: 24499210]
[81]
Lagousi T, Basdeki P, Routsias J, Spoulou V. Novel protein-based pneumococcal vaccines: Assessing the use of distinct protein fragments instead of full-length proteins as vaccine antigens. Vaccines (Basel) 2019; 7(1)E9
[http://dx.doi.org/10.3390/vaccines7010009] [PMID: 30669439]
[82]
Seabright GE, Doores KJ, Burton DR, Crispin M. Protein and glycan mimicry in HIV vaccine design. J Mol Biol 2019; S0022- 2836(19): 30212-8.
[http://dx.doi.org/10.1016/j.jmb.2019.04.016] [PMID: 31028779]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 2
Year: 2019
Page: [75 - 84]
Pages: 10
DOI: 10.2174/1570162X17666190618160608
Price: $58

Article Metrics

PDF: 39
HTML: 5