Efficacy of a multigenic protein vaccine containing multimeric HIV gp160 against heterologous SHIV clade C challenges

Rasmussen, Robert A.; Ong, Helena; Song, Ruijiang; Chenine, Agnès Laurence; Ayash-Rashkovsky, Mila; Hu, Shiu Lok; Polacino, Patricia; Else, James G.; Novembre, Francis J.; Ruprecht, Ruth M.

doi:10.1097/qad.0b013e32828684ea

Cited by 23 publications

(47 citation statements)

References 24 publications

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“…Nevertheless, SHIV-1157ipd3N4 has been used successfully to assess the efficacy of a multigenic DNA prime/protein boost and a multigenic protein-only vac-cine (44). The following parameters have been used as readouts of vaccine efficacy: complete protection from systemic viral infection, as well as delay and lowering of peak viremia.…”

Section: Discussionmentioning

confidence: 99%

“…The neutralization sensitivity of SHIV-2873Nip was determined using both PBMC-based and TZM-bl reporter cell line-based neutralization assays, as described previously (11,19,24,44,51). In both cases, serial dilutions of either RM sera or MAbs were set up in triplicate in 96-well plates, and virus was added (50 to 200 TCID 50 ) and incubated for 1 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…However, the majority of current SHIV strains utilize envelope genes derived from HIV clade B strains, which represent fewer than 10% of all global infections. Therefore, the available SHIV chimeras do not reflect the genetic diversity of the HIV epidemic, which is dominated by non-B clades, especially by HIV-C. Only a few studies have focused on developing anti-clade C Env vaccines (25,27,44,49), with one efficacy study in primate models (44). To investigate lentiviral pathogenesis as well as anti-HIV-C vaccine safety and efficacy in nonhuman primate models, a pathogenic, CCR5-restricted, clade C SHIV (SHIV-C) would be very useful.…”

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confidence: 99%

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Neutralization-Sensitive R5-Tropic Simian-Human Immunodeficiency Virus SHIV-2873Nip, Which Carries env Isolated from an Infant with a Recent HIV Clade C Infection

Siddappa

Song

Kramer

et al. 2009

J Virol

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Human immunodeficiency virus clade C (HIV-C) accounts for >56% of all HIV infections worldwide. To investigate vaccine safety and efficacy in nonhuman primates, a pathogenic, R5-tropic, neutralization-sensitive simian-human immunodeficiency virus (SHIV) carrying HIV-C env would be desirable. We have constructed SHIV-2873Ni, an R5-tropic SHIV carrying a primary pediatric HIV-C env gene isolated from a 2-month-old Zambian infant, who died within 1 year of birth. SHIV-2873Ni was constructed using SHIV-1157ipd3N4 (R.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Neutralization-Sensitive R5-Tropic Simian-Human Immunodeficiency Virus SHIV-2873Nip, Which Carries env Isolated from an Infant with a Recent HIV Clade C Infection

Siddappa

Song

Kramer

et al. 2009

J Virol

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“…Table 1 examined in this study and lists the immunogens and challenge viruses used. The levels of protection are given according to the original publications (15)(16)(17), with minor changes for vaccinees RGe-11 and RFo-11 and control animal RAk-11 (15) since only immune responses during the low-dose challenge phase were analyzed in the present study. For all vaccinees, plasma samples collected at two different time points were evaluated for Ab responses: week 0, after the completion of all immunizations but before the first virus challenge, and week 7, after multiple live-virus exposures.…”

Section: Animalsmentioning

confidence: 99%

“…We studied Indian-origin RMs (Macaca mulatta) that had been enrolled in three different vaccine/challenge studies described elsewhere (15)(16)(17). They were housed at the Yerkes Regional Primate Research Center (Atlanta, GA), and all procedures were approved by the Animal Care and Use Committees of Emory University and the Dana-Farber Cancer Institute (DFCI).…”

Section: Animalsmentioning

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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No acquisition: A new ambition for HIV vaccine development?

Lakhashe

Silvestri

Ruprecht

2011

Current Opinion in Virology

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Development of a safe and effective prophylactic HIV-1 vaccine presents unique challenges. The pessimism following the failure of two HIV-1 vaccine concepts in clinical trials, HIV-1 gp120 and an adenovirus-based approach to induce only cellular immune responses, has been replaced by cautious optimism engendered by the RV144 trial outcome, the isolation of several new broadly reactive neutralizing monoclonal antibodies, and recent primate model data indicating prevention of viral acquisition by active or passive immunization. Intense efforts are underway to optimize immunogen design, adjuvants, and the tools for preclinical evaluation of candidate vaccines in primates, where correlates of protection can be examined in detail – as proof-of-concept for clinical trials.

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Efficacy of a multigenic protein vaccine containing multimeric HIV gp160 against heterologous SHIV clade C challenges

Abstract: Protein-only immunogens induced significant protection against heterologous viruses encoding env from locally circulating viruses.

Cited by 23 publications

References 24 publications

Neutralization-Sensitive R5-Tropic Simian-Human Immunodeficiency Virus SHIV-2873Nip, Which Carries env Isolated from an Infant with a Recent HIV Clade C Infection

Neutralization-Sensitive R5-Tropic Simian-Human Immunodeficiency Virus SHIV-2873Nip, Which Carries env Isolated from an Infant with a Recent HIV Clade C Infection

Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine Protection

No acquisition: A new ambition for HIV vaccine development?

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