Gp120-Alum Boosting of a Gag-Pol-Env DNA/MVA AIDS Vaccine: Poorer Control of a Pathogenic Viral Challenge

Buge, Suzan L.; Ma, Huiyuan; Amara, Rama Rao; Wyatt, Linda S.; Earl, Patricia L.; Villinger, François; Montefiori, David C.; Staprans, Silvija I.; Xu, Yixin; Carter, Eddye; O’Neil, Shawn P.; Herndon, James G.; Hill, Elizabeth M.; Moss, Bernard; Robinson, Harriet L.; McNicholl, Janet M.

doi:10.1089/088922203322493067

Cited by 29 publications

(17 citation statements)

References 32 publications

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“…In another study using our Gag-Pol-Env DNA/MVA vaccine, seven additional non-A*01 macaques were protected (12). For adeno5-vectored vaccines, protection against SHIV-89.6P has been much more uniform for A*01 macaques than for non-A*01 macaques (25,29).…”

Section: Vol 79 2005 Long-term Control Of Shiv By a Low T-cell Respmentioning

confidence: 94%

Signature for Long-Term Vaccine-Mediated Control of a Simian and Human Immunodeficiency Virus 89.6P Challenge: Stable Low-Breadth and Low-Frequency T-Cell Response Capable of Coproducing Gamma Interferon and Interleukin-2

Sadagopal

Amara

Montefiori

et al. 2005

J Virol

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Section: Vol 79 2005 Long-term Control Of Shiv By a Low T-cell Respmentioning

confidence: 94%

Signature for Long-Term Vaccine-Mediated Control of a Simian and Human Immunodeficiency Virus 89.6P Challenge: Stable Low-Breadth and Low-Frequency T-Cell Response Capable of Coproducing Gamma Interferon and Interleukin-2

Sadagopal

Amara

Montefiori

et al. 2005

J Virol

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“…7 We also found that adding gp120 protein boosters in alum to our Gag-Pol-Env DNA/MVA protocols decreased protection. 8 Based on these findings we have undertaken the development of clade B HIV Gag-Pol-Env DNA and MVA immunogens for an HIV-1/AIDS vaccine for humans.…”

Section: Introductionmentioning

confidence: 99%

Multiprotein HIV Type 1 Clade B DNA/MVA Vaccine: Construction, Safety, and Immunogenicity in Macaques

Smith

Amara²,

McClure³

et al. 2004

AIDS Research and Human Retroviruses

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Recently, a simian/human immunodeficiency virus (SHIV) vaccine consisting of priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vaccinia Ankara (rMVA) has successfully controlled a virulent SHIV challenge in a macaque model. In this, and the accompanying paper, we report on the construction and testing of a Gag-Pol-Env DNA/MVA vaccine for HIV-1/AIDS. The DNA vaccine, pGA2/JS2, expresses aggregates of Gag proteins and includes safety mutations that render it integration, reverse transcription, and packaging defective. The rMVA vaccine, MVA/HIV 48, is integration and reverse transcription defective and has a truncated Env to enhance expression on the plasma membrane. In a study in rhesus macaques, priming with pGA2/JS2 and boosting with MVA/HIV 48 raised high frequencies of T cells for Gag and Env and lower frequencies of T cells for PR, RT, and Tat. Stimulations with five peptide pools for Gag and seven peptide pools for Env revealed epitopes for cellular immune responses throughout Gag and Env. On average, CD4 T cells from the vaccinated animals recognized 7.1 peptide pools and CD8 T cells, 3.2 peptide pools. Both the height and the breadth of the elicited cellular response provide hope that this multiprotein DNA/MVA vaccine will successfully control clade B isolates of HIV-1, as well as contribute to the control of other clades and recombinant forms of HIV-1/AIDS.

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“…HIV-1 gp120 was also found to inhibit major histocompatibility complex (MHC) class I presentation of Tcell epitopes of other antigen in vitro (14). More importantly, there is evidence that vaccination with gp120 can enhance viral replication and even decrease protection provided by other antigens (4,25). In a recent study the HIV envelope was reported to reduce the immune responses elicited against the HIV gag antigen by an unknown mechanism (27).…”

mentioning

confidence: 99%

X4 Human Immunodeficiency Virus Type 1 gp120 Down-Modulates Expression and Immunogenicity of Codelivered Antigens

Hovav

Santosuosso

Bivas-Benita

et al. 2009

J Virol

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In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120 protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120 alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin in a mouse model. We found that the presence of gp120 leads to a significant reduction in the expression level of the codelivered antigen in vivo. Antigen presentation by antigen-presenting cells was also reduced and resulted in the induction of weak antigen-specific cellular and humoral immune responses. Importantly, gp120-mediated immune interference was observed after administration of the plasmids at the same or at distinct locations. To characterize the region in gp120 mediating these effects, we used plasmid constructs encoding gp120 that lacks the V1V2 loops (⌬V1V2) or the V3 loop (⌬V3). After immunization, the ⌬V1V2, but not the ⌬V3 construct, was able to reduce antigen expression, antigen presentation, and subsequently the immunogenicity of the codelivered antigen. The V3 loop dependence of this phenomenon seems to be limited to V3 loops known to interact with the CXCR4 molecule but not with CCR5. Our study presents a novel mechanism by which HIV-1 gp120 interferes with the immune response against coadministered antigen in a polyvalent vaccine preparation.

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Gp120-Alum Boosting of a Gag-Pol-Env DNA/MVA AIDS Vaccine: Poorer Control of a Pathogenic Viral Challenge

Cited by 29 publications

References 32 publications

Signature for Long-Term Vaccine-Mediated Control of a Simian and Human Immunodeficiency Virus 89.6P Challenge: Stable Low-Breadth and Low-Frequency T-Cell Response Capable of Coproducing Gamma Interferon and Interleukin-2

Signature for Long-Term Vaccine-Mediated Control of a Simian and Human Immunodeficiency Virus 89.6P Challenge: Stable Low-Breadth and Low-Frequency T-Cell Response Capable of Coproducing Gamma Interferon and Interleukin-2

Multiprotein HIV Type 1 Clade B DNA/MVA Vaccine: Construction, Safety, and Immunogenicity in Macaques

X4 Human Immunodeficiency Virus Type 1 gp120 Down-Modulates Expression and Immunogenicity of Codelivered Antigens

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