2013
DOI: 10.1371/journal.pone.0075665
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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

Abstract: Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential to mediate antiviral effector functions that could be beneficial to vaccine-induced protection. Here, plasma IgG responses were assessed in three HIV-1 gp120 vaccine efficacy trials (RV144, Vax003, Vax004) and in HIV-1-infected individuals by using arrays of overlapping peptides spanning the entire consensus gp160 of all major genetic subtypes and circulating recombinant forms (CRFs) of the virus. In … Show more

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Cited by 220 publications
(298 citation statements)
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“…124 IgGs to linear epitopes in the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to protection in RV144. 125 These correlates were supported by corresponding V2 mutations in a "sieve" analysis of breakthrough viruses suggesting that genetic mutations away from V2 sequences found in the vaccine (positions 169K and 181I) were associated with altered efficacy. Combination of lamivudine and zidovudine (Combivir), efavirenz, atazanavir, nevirapine, tenofovir, lamivudine, zidovudine, didanosine, stavudine, combination of lopinavir and ritonavir (Kaletra and Aluvia), ritonavir, and combination of emtricitabine and tenofovir (Truvada).…”
Section: Hiv Vaccine Clinical Developmentmentioning
confidence: 86%
“…124 IgGs to linear epitopes in the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to protection in RV144. 125 These correlates were supported by corresponding V2 mutations in a "sieve" analysis of breakthrough viruses suggesting that genetic mutations away from V2 sequences found in the vaccine (positions 169K and 181I) were associated with altered efficacy. Combination of lamivudine and zidovudine (Combivir), efavirenz, atazanavir, nevirapine, tenofovir, lamivudine, zidovudine, didanosine, stavudine, combination of lopinavir and ritonavir (Kaletra and Aluvia), ritonavir, and combination of emtricitabine and tenofovir (Truvada).…”
Section: Hiv Vaccine Clinical Developmentmentioning
confidence: 86%
“…24). Protection correlated with antibodies against the V1/V2 region of gp120 (25), particularly those antibodies of the IgG3 subclass that mediate potent antibody-dependent cellular cytotoxicity (ADCC) (26), in addition to other aspects of anti-gp120 humoral immunity (25)(26)(27)(28)(29). Importantly, efficacy in the RV144 trial was temporally dependent, peaking at ∼59.9% early in the study and waning to background by the end of the 3-y postvaccination follow-up, thus producing an overall efficacy of 31.2% (30).…”
mentioning
confidence: 95%
“…These results along with a recent sieve analysis 64 generate the hypothesis that IgG to linear epitopes in the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to protection in RV144. 65 Approximately 90% of incident infections in RV144 were CRF01_AE, the predominant circulating strain in much of South East Asia. A sieve analysis identified 2 vaccine-associated genetic signatures in V2 corresponding to sites 169 and 181, further supporting the hypothesis that vaccination-induced immune responses directed against the V2 loop were associated with protection.…”
Section: Correlates Of Protection-new Perspectivesmentioning
confidence: 99%