Lessons learned from HIV-1 vaccine trials: new priorities and directions

McMichael, Andrew J.; Haynes, Barton F.

doi:10.1038/ni.2264

Cited by 83 publications

(70 citation statements)

References 63 publications

(88 reference statements)

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“…Other approaches focus on B regulation, such as self-tolerance (27,28) and suspected immunosuppressive properties of gp120 (29)(30)(31). Another recent approach is the recruitment of germ line and intermediate B cell precursors involved in the production of bnAbs (32)(33)(34). As new vaccine concepts enter preclinical and clinical phases of testing, it will be important to compare the magnitudes and breadths of nAb responses using a relevant spectrum of HIV-1 variants that are representative of the global epidemic.…”

mentioning

confidence: 99%

Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies

deCamp

Hraber

Bailer

et al. 2014

J Virol

300

395

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IMPORTANCEAn effective HIV-1 vaccine will need to overcome the extraordinary genetic variability of the virus, where most variation occurs in the viral envelope glycoproteins that are the sole targets for neutralizing antibodies. Efforts to elicit broadly cross-reactive neutralizing antibodies that will protect against infection by most circulating strains of the virus are guided in part by in vitro assays that determine the ability of vaccine-elicited antibodies to neutralize genetically diverse HIV-1 variants. Until now, little information was available on how many and which strains of the virus are best suited for this purpose. We applied robust statistical methods to evaluate a large neutralization data set and identified a small panel of viruses that are a good representation of the global epidemic. The neutralization properties of this new panel of reference strains should facilitate the development of an effective HIV-1 vaccine.

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mentioning

confidence: 99%

Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies

deCamp

Hraber

Bailer

et al. 2014

J Virol

300

395

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“…In order to improve future vaccine candidates, it is important to understand the protective mechanism(s) leading to reduced virus acquisition (1). Thus, correlates of infection risk for the recent RV144 vaccine efficacy trial (2) are the subject of intense study (3,4). However, additional information can be gained by dissecting immune responses in biologically relevant animal models where immunization induced complete protection from immunodeficiency virus challenge(s) (5, 6).…”

mentioning

confidence: 99%

Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine Protection

Bachler

Humbert

Palikuqi

et al. 2013

J Virol

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cIdentifying immune correlates of protection is important to develop vaccines against infectious diseases. We designed a novel, universally applicable strategy to profile the antibody (Ab) repertoire of protected vaccine recipients, using recombinant phages encoding random peptide libraries. The new approach, termed "protection-linked (PL) biopanning," probes the Ab paratopes of protected vaccinees versus those with vaccine failure. As proof of concept, we screened plasma samples from vaccinated rhesus macaques (RMs) that had completely resisted multiple mucosal challenges with R5-tropic simian-human immunodeficiency viruses (SHIVs). The animals had been immunized with a multicomponent vaccine (multimeric HIV-1 gp160, HIV-1 Tat, and SIV Gag-Pol particles). After PL biopanning, we analyzed the phagotopes selected for amino acid homologies; in addition to the expected Env mimotopes, one recurring motif reflected the neutralizing Ab epitope at the N terminus (NT) of HIV-1 Tat. Subsequent binding and functional assays indicated that anti-Tat NT Abs were present only in completely or partially protected RMs; peak viremia of the latter was inversely correlated with anti-Tat NT Ab titers. In contrast, highly viremic, unvaccinated controls did not develop detectable Abs against the same epitope. Based upon the protective effect observed in vivo, we suggest that Tat should be included in multicomponent HIV-1 vaccines. Our data highlight the power of the new PL-biopanning strategy to identify Ab responses with significant association to vaccine protection, regardless of the mechanism(s) or targets of the protective Abs. PL biopanning is also unbiased with regard to pathogens or disease model, making it a universal tool.T he design of a safe, effective vaccine is desirable to control the AIDS pandemic. In order to improve future vaccine candidates, it is important to understand the protective mechanism(s) leading to reduced virus acquisition (1). Thus, correlates of infection risk for the recent RV144 vaccine efficacy trial (2) are the subject of intense study (3,4). However, additional information can be gained by dissecting immune responses in biologically relevant animal models where immunization induced complete protection from immunodeficiency virus challenge(s) (5, 6).Recent results of active (7,8) and passive (9) immunization trials in humans and in nonhuman primates suggested that antihuman immunodeficiency virus type 1 (HIV-1) Env antibodies (Abs) can have protective roles even in the absence of virus neutralization, implying that other Ab-mediated mechanisms may be involved in preventing mucosal virus acquisition. Thus, the ability to profile Ab epitopes associated with protection might help to identify potential targets for future HIV-1 vaccines.Random peptide phage display has been used to dissect Ab responses in the context of primate immunodeficiency virus infections, and several studies have identified HIV-1 or simian-human immunodeficiency virus (SHIV)-specific peptides (10-14). We developed a novel epitope...

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“…Modeller is a computer program that models three-dimensional structures of proteins and their assemblies by satisfaction of spatial restraints [14][15][16][17] . The field has jumped from an early start using recombinant soluble antigen based upon the surface envelope glycoprotein (Env) gp120 to elicit antibody response, to focus on cytotoxic T cell (CTL)-based vaccine design 25,26 . However, progress in two areas has galvanized the HIV-1 vaccine field into an unprecedented sense of purpose and activity.…”

Section: Homology Modelingmentioning

confidence: 99%

Untitled

2014

IJPSR

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ABSTRACT:The development of a highly effective AIDS vaccine will depend on the success of designing immunogens that will elicit immune response against broadly neutralizing antibodies to naturally circulating strains of HIV-can be done by reverse vaccinology. Reverse vaccinology is a good approach for provoking the broadly neutralizing antibody response by identifying the specific epitopes i.e. surface proteins. The 3D structure of a protein is a prerequisite for structure based drug design as well as for identifying the conformational epitopes that are essential for the designing vaccines.

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Lessons learned from HIV-1 vaccine trials: new priorities and directions

Cited by 83 publications

References 63 publications

Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies

Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies

Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine Protection

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