Role of Human Immunodeficiency Virus Type 1 Envelope Structure in the Induction of Broadly Neutralizing Antibodies

Benjelloun, Fahd; Lawrence, Philip; Verrier, Bernard; Genin, Christian; Paul, Stéphane

doi:10.1128/jvi.01110-12

Cited by 23 publications

(17 citation statements)

References 161 publications

(222 reference statements)

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“…A subset of very potent bNAb recognizes a V2V3 quaternary determinant (84)(85)(86). These antibodies, though overlapping in V2 binding with RV144-associated mAb, have substantially greater neutralizing capacity and highly mutated the VDJ (variable, diverse, joining) gene segments of the heavy chains of immunoglobulins and extended CDR3 regions (87). Interestingly, one of the two gp120 Envs in AIDSVAX R B/E binds to all these reagents and to the putative germline sequences (84) from which a subset of this V2V3 bNAb derives.…”

Section: Unanswered Questionsmentioning

confidence: 99%

Lessons from the RV144 Thai Phase III HIV-1 Vaccine Trial and the Search for Correlates of Protection

2015

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RV144 remains the only HIV-1 vaccine trial to demonstrate efficacy against HIV-1 acquisition. The prespecified analysis of immune correlates of risk showed that antibodies directed against the V1V2 region of gp120, in particular the IgG1 and IgG3 subclass mediating antibody-dependent cell-mediated cytotoxicity, seem to play a predominant role in protection against HIV-1 acquisition and that plasma envelope (Env)-specific IgA antibodies were directly correlated with risk. RV144 and recent nonhuman primate challenge studies suggest that Env is essential, and perhaps sufficient, to induce protective antibody responses against mucosal HIV-1 acquisition. Follow-up clinical trials are ongoing to further dissect the immune responses elicited by the RV144 ALVAC-HIV and AIDSVAX® B/E regimen. The study of gp120 Env immunogens and immune correlates of risk has resulted in the development of improved antigens. Whether the RV144 immune correlates of risk will generalize to other populations vaccinated with similar immunogens with different modes and intensity of transmission remains to be demonstrated. Efficacy trials are now planned in heterosexual populations in southern Africa and men who have sex with men in Thailand.

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Section: Unanswered Questionsmentioning

confidence: 99%

Lessons from the RV144 Thai Phase III HIV-1 Vaccine Trial and the Search for Correlates of Protection

2015

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“…However, it remains unclear how a vaccine can elicit antibodies that will recognize the substantial heterogeneity of Env sequences globally. Moreover, HIV‐1 has other mechanisms to evade the humoral immune system, including low Env spike density on the virion surface, heavy glycosylation, conformational shielding of highly conserved Env epitopes, and mimicry of Env carbohydrates and proteins of host molecules .…”

Section: A Global Vaccine Needs a Global Reachmentioning

confidence: 99%

“…For example, several laboratories have used previously identified antibodies, such as the V1V2‐directed antibodies PG9, PG16, and CH01‐CH04, to screen for binding to gp120 envelope monomers which can then be developed into potential immunogen candidates . Other researchers have centered on designing Env immunogens to elicit antibodies that resemble the VRC01 antibody, which binds the highly conserved conformational CD4 binding site . Protein scaffolds have also been used to express neutralizing epitopes .…”

Section: Strategies For a Global Hiv‐1 Vaccinementioning

confidence: 99%

A global approach to HIV‐1 vaccine development

Stephenson

Barouch

2013

Immunological Reviews

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Summary A global human immunodeficiency virus-1 (HIV-1) vaccine will have to elicit immune responses capable of providing protection against a tremendous diversity of HIV-1 variants. In this review, we first describe the current state of the HIV-1 vaccine field, outlining the immune responses that are desired in a global HIV-1 vaccine. In particular, we emphasize the likely importance of Env-specific neutralizing and non-neutralizing antibodies for protection against HIV-1 acquisition and the likely importance of effector Gag-specific T lymphocytes for virologic control. We then highlight four strategies for developing a global HIV-1 vaccine. The first approach is to design specific vaccines for each geographic region that include antigens tailor-made to match local circulating HIV-1 strains. The second approach is to design a vaccine that will elicit Env-specific antibodies capable of broadly neutralizing all HIV-1 subtypes. The third approach is to design a vaccine that will elicit cellular immune responses that are focused on highly conserved HIV-1 sequences. The fourth approach is to design a vaccine to elicit highly diverse HIV-1-specific responses. Finally, we emphasize the importance of conducting clinical efficacy trials as the only way to determine which strategies will provide optimal protection against HIV-1 in humans.

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“…Despite emerging insights from studies of exposed uninfected individuals (1,2), much of the global research effort has necessarily focused on individuals who exhibit a degree of viral suppression, such as elite controllers and longterm nonprogressors (3). It is clear from these studies that CD8 T cells play a critical role in the containment of HIV replication (4).…”

mentioning

confidence: 99%

Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations

Hill

Darrah

Ende

et al. 2014

The Journal of Immunology

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Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2Kd epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2Dd epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2Dd specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.

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Role of Human Immunodeficiency Virus Type 1 Envelope Structure in the Induction of Broadly Neutralizing Antibodies

Cited by 23 publications

References 161 publications

Lessons from the RV144 Thai Phase III HIV-1 Vaccine Trial and the Search for Correlates of Protection

Lessons from the RV144 Thai Phase III HIV-1 Vaccine Trial and the Search for Correlates of Protection

A global approach to HIV‐1 vaccine development

Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations

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