The Use of Nonhuman Primate Models in HIV Vaccine Development

Morgan, Cecilia; Marthas, Marta; Miller, Christopher J.; Duerr, Ann; Cheng‐Mayer, Cecilia; Desrosiers, Ronald C.; Flores, Jorge; Haigwood, Nancy L.; Hu, Shiu Lok; Johnson, R.P.; Lifson, Jeffrey D.; Montefiori, David C.; Moore, John P.; Robert-Guroff, Marjorie; Robinson, Harriet L.; Self, Steven G.; Corey, Lawrence

doi:10.1371/journal.pmed.0050173

Cited by 87 publications

(100 citation statements)

References 12 publications

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“…This issue has recently been recognized as one for which there is a lack of data and knowledge in the HIV vaccine development field (9,27). Here we provide such data in the context of clade C HIV-1 immunogens administered by DNA priming and NYVAC boosting using identical vaccine lots and protocols in both species.…”

Section: Vol 83 2009 Comparative Vaccine Responses In Macaques and mentioning

confidence: 98%

“…A debate has ensued in the field as to whether the rhesus macaque model should be considered a "gatekeeper" for promising HIV vaccine candidates as they progress toward human trials (27). Although many HIV vaccine concepts and prototypes have been evaluated in rhesus macaques, significant changes invariably occur when these vaccine candidates are refined and prepared for use in human trials.…”

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confidence: 99%

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Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens

Mooij

Balla-Jhagjhoorsingh

Beenhakker

et al. 2009

J Virol

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Rhesus macaques (Macaca؉ and CD8 ؉ T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-␥, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN-␥ T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved.

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Section: Vol 83 2009 Comparative Vaccine Responses In Macaques and mentioning

confidence: 98%

mentioning

confidence: 99%

Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens

Mooij

Balla-Jhagjhoorsingh

Beenhakker

et al. 2009

J Virol

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show abstract

“…This challenge requires careful measurement of these responses in all future vaccine studies, where nonhuman primate models will be key tools in identifying vaccine strategies that favor protection over infection. The lack of efficacy and increased transmission in the Step and Phambili trials sparked significant debate about the usefulness of nonhuman primate models in HIV vaccine development (85)(86)(87)(88)(89)(90)(91)(92)(93). Despite the obvious limitations of any animal model of human disease, nonhuman primate studies provided at least one overlooked clue that presaged the likelihood of increased risk in the Step and Phambili trials.…”

Section: Strategies To Elicit Continuous Protection Against Hiv By Vamentioning

confidence: 99%

Antibody persistence and T-cell balance: Two key factors confronting HIV vaccine development

Lewis

DeVico

Gallo

2014

Proc. Natl. Acad. Sci. U.S.A.

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The quest for a prophylactic AIDS vaccine is ongoing, but it is now clear that the successful vaccine must elicit protective antibody responses. Accordingly, intense efforts are underway to identify immunogens that elicit these responses. Regardless of the mechanism of antibodymediated protection, be it neutralization, Fc-mediated effector function, or both, antibody persistence and appropriate T-cell help are significant problems confronting the development of a successful AIDS vaccine. Here, we discuss the evidence illustrating the poor persistence of antibody responses to Env, the envelope glycoprotein of HIV-1, and the related problem of CD4 + T-cell responses that compromise vaccine efficacy by creating excess cellular targets of HIV-1 infection. Finally, we propose solutions to both problems that are applicable to all Envbased AIDS vaccines regardless of the mechanism of antibody-mediated protection.

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“…Nonhuman primate AIDS models are important for the analysis of AIDS pathogenesis and the evaluation of vaccine efficacy (5,35,47). Models of simian immunodeficiency virus (SIV) infection in macaques are widely used currently (12,22).…”

Section: Irus-specific Cd8mentioning

confidence: 99%

Association of Major Histocompatibility Complex Class I Haplotypes with Disease Progression after Simian Immunodeficiency Virus Challenge in Burmese Rhesus Macaques

Nomura

Yamamoto

Shiino

et al. 2012

J Virol

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Nonhuman primate AIDS models are essential for the analysis of AIDS pathogenesis and the evaluation of vaccine efficacy. Multiple studies on human immunodeficiency virus and simian immunodeficiency virus (SIV) infection have indicated the association of major histocompatibility complex class I (MHC-I) genotypes with rapid or slow AIDS progression. The accumulation of macaque groups that share not only a single MHC-I allele but also an MHC-I haplotype consisting of multiple polymorphic MHC-I loci would greatly contribute to the progress of AIDS research. Here, we investigated SIVmac239 infections in four groups of Burmese rhesus macaques sharing individual MHC-I haplotypes, referred to as A, E, B, and J. Out of 20 macaques belonging to A + ( n = 6), E + ( n = 6), B + ( n = 4), and J + ( n = 4) groups, 18 showed persistent viremia. Fifteen of them developed AIDS in 0.5 to 4 years, with the remaining three at 1 or 2 years under observation. A + animals, including two controllers, showed slower disease progression, whereas J + animals exhibited rapid progression. E + and B + animals showed intermediate plasma viral loads and survival periods. Gag-specific CD8 + T-cell responses were efficiently induced in A + animals, while Nef-specific CD8 + T-cell responses were in A + , E + , and B + animals. Multiple comparisons among these groups revealed significant differences in survival periods, peripheral CD4 + T-cell decline, and SIV-specific CD4 + T-cell polyfunctionality in the chronic phase. This study indicates the association of MHC-I haplotypes with AIDS progression and presents an AIDS model facilitating the analysis of virus-host immune interaction.

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The Use of Nonhuman Primate Models in HIV Vaccine Development

Abstract: Cecilia Morgan and colleagues outline a two-stage nonhuman primate screening strategy for T cell-based HIV-1 vaccines.

Cited by 87 publications

References 12 publications

Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens

Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens

Antibody persistence and T-cell balance: Two key factors confronting HIV vaccine development

Association of Major Histocompatibility Complex Class I Haplotypes with Disease Progression after Simian Immunodeficiency Virus Challenge in Burmese Rhesus Macaques

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