[Viewpoint] A tale of four studies: HIV vaccine immunogenicity and efficacy in clinical trials

1.Gray GE Bekker LG Laher F et al.

Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120-MF59 in adults.

N Engl J Med. 2021; 384: 1089-11002.Pitisuttithum P Gilbert P Gurwith M et al.

Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand.

J Infect Dis. 2006; 194: 1661-16713.Gilbert PB Peterson ML Follmann D et al.

Correlation between immunologic responses to a recombinant glycoprotein 120 vaccine and incidence of HIV-1 infection in a phase 3 HIV-1 preventive vaccine trial.

J Infect Dis. 2005; 191: 666-6774.Buchbinder SP Mehrotra DV Duerr A et al.

Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial.

Lancet. 2008; 372: 1881-18935.Gray GE Allen M Moodie Z et al.

Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study.

Lancet Infect Dis. 2011; 11: 507-5156.Hammer SM Sobieszczyk ME Janes H et al.

Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine.

N Engl J Med. 2013; 369: 2083-20927.Rerks-Ngarm S Pitisuttithum P Nitayaphan S et al.

Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.

N Engl J Med. 2009; 361: 2209-22208.Gray GE Huang Y Grunenberg N et al.

Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa.

Sci Transl Med. 2019; 11eaax18809.Bekker LG Moodie Z Grunenberg N et al.

Subtype C ALVAC-HIV and bivalent subtype C gp120/MF59 HIV-1 vaccine in low-risk, HIV-uninfected, South African adults: a phase 1/2 trial.

Lancet HIV. 2018; 5: e366-e37810.Haynes BF Gilbert PB McElrath MJ et al.

Immune-correlates analysis of an HIV-1 vaccine efficacy trial.

N Engl J Med. 2012; 366: 1275-128611.Zolla-Pazner S deCamp AC Cardozo T et al.

Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial.

PLoS One. 2013; 8e5362912.Zolla-Pazner S deCamp A Gilbert PB et al.

Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.

PLoS One. 2014; 9e8757213.Gottardo R Bailer RT Korber BT et al.

Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial.

PLoS One. 2013; 8e7566514.Chung AW Ghebremichael M Robinson H et al.

Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines.

Sci Transl Med. 2014; 6228ra3815.Yates NL Liao HX Fong Y et al.

Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination.

Sci Transl Med. 2014; 6228ra3916.Gartland AJ Li S McNevin J et al.

Analysis of HLA A*02 association with vaccine efficacy in the RV144 HIV-1 vaccine trial.

J Virol. 2014; 88: 8242-825518.

Combo of two HIV vaccines fails its big test.

Science. 2020; 367: 611-61219.Zhao LP Fiore-Gartland A Carpp LN et al.

Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans.

PLoS One. 2020; 15e022680320.Vaccari M Gordon SN Fourati S et al.

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

Nat Med. 2016; 22: 762-77021.Pitisuttithum P Nitayaphan S Chariyalertsak S et al.

Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial.

Lancet HIV. 2020; 7: e238-e24822.Vandormael A Akullian A Siedner M de Oliveira T Bärnighausen T Tanser F

Declines in HIV incidence among men and women in a South African population-based cohort.

Nat Commun. 2019; 10548223.Robb ML Eller LA Kibuuka H et al.

Prospective study of acute HIV-1 infection in adults in east Africa and Thailand.

N Engl J Med. 2016; 374: 2120-213024.Tshabalala M Mellet J Pepper MS

Human leukocyte antigen diversity: a southern African perspective.

J Immunol Res. 2015; 201574615125.Hurley CK Kempenich J Wadsworth K et al.

Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0.

HLA. 2020; 95: 516-53126.Gandhi RT Bosch RJ Rangsin R et al.

HLA class I alleles associated with mortality in Thai military recruits with HIV-1 CRF01_AE infection.

AIDS Res Hum Retroviruses. 2016; 32: 44-4927.Sivro A Schuetz A Sheward D et al.

Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes.

Sci Transl Med. 2018; 10eaam635428.Haaland RE Hawkins PA Salazar-Gonzalez J et al.

Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1.

PLoS Pathog. 2009; 5e100027429.Tunthanathip P Lolekha R Bollen LJ et al.

Indicators for sexual HIV transmission risk among people in Thailand attending HIV care: the importance of positive prevention.

Sex Transm Infect. 2009; 85: 36-4130.Looker KJ Welton NJ Sabin KM et al.

Global and regional estimates of the contribution of herpes simplex virus type 2 infection to HIV incidence: a population attributable fraction analysis using published epidemiological data.

Lancet Infect Dis. 2020; 20: 240-24931.Kouyoumjian SP Heijnen M Chaabna K et al.

Global population-level association between herpes simplex virus 2 prevalence and HIV prevalence.

AIDS. 2018; 32: 1343-135232.Neidich SD Fong Y Li SS et al.

Antibody Fc effector functions and IgG3 associate with decreased HIV-1 risk.

J Clin Invest. 2019; 129: 4838-4849

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