Reduction of Anti-HIV-1 Gag Immune Responses During Co-Immunization: Immune Interference by the HIV-1 Envelope

Toapanta, Franklin R.; Craigo, Jodi K.; Montelaro, Ronald C.; Ross, Ted M.

doi:10.2174/157016207780077057

Cited by 27 publications

(21 citation statements)

References 84 publications

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“…However, the mean value of Gag specific CD4C and CD8C T cells decreased after immunization of rLaSota/gp160 together with rLaSota/optGag compared to immunization with rLaSota/opt Gag alone. The gp160 mediated suppression of CD4C and CD8C T cell responses against Gag could be due to various reasons as reported in various findings reported previously (1) competition of expression resulting in immunodominance of Env over Gag; 36 (2) suppression of expression via type1 IFN; 37 (3) Env-mediated suppression of dendritic cell activation and maturation; 38 and (4) epitope competition for H-2 d MHC class I presentation especially in case of CD8C T cell suppression. 39,40 Further, inclusion of rLasota/optGag with rLaSota/gp160, rLaSota/gp140L and rLaSota/gp140S enhanced Env-specific IFN-g-producing CD4C and CD8C T cells compared to the Env expressing rNDVs inoculated alone in our previous study.…”

Section: Increase Cd4mentioning

confidence: 79%

Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus

Khattar

Palaniyandi

Samal

et al. 2015

Human Vaccines & Immunotherapeutics

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The combination of multiple HIV antigens in a vaccine can broaden antiviral immune responses. In this study, we used NDV vaccine strain LaSota to generate rNDV (rLaSota/optGag) expressing human codon optimized p55 Gag protein of HIV-1. We examined the effect of co-immunization of rLaSota/optGag with rNDVs expressing different forms of Env protein gp160, gp120, gp140L [a version of gp140 that lacked cytoplasmic tail and contained complete membrane-proximal external region (MPER)] and gp140S (a version of gp140 that lacked cytoplasmic tail and distal half of MPER) on magnitude and breadth of humoral, mucosal and cellular immune responses in guinea pigs and mice. Our results showed that inclusion of rLaSota/optGag with rNDVs expressing different forms of Env HIV Gag did not affect the Env-specific humoral and mucosal immune responses in guinea pigs and that the potent immune responses generated against Env persisted for at least 13 weeks post immunization. The highest Env-specific humoral and mucosal immune responses were observed with gp140SCoptGag group. The neutralizing antibody responses against HIV strains BaL.26 and MN.3 induced by gp140SCoptGag and gp160CoptGag were higher than those elicited by other groups. Inclusion of Gag with gp160, gp140S and gp140L enhanced the level of Env-specific IFN-g-producing CD8C T cells in mice. Inclusion of Gag with gp160 and gp140L also resulted in increased Env-specific CD4 C T cells. The level of Gag-specific CD8C and CD4 C T cells was also enhanced in mice immunized with Gag along with gp140S and gp120. These results indicate lack of antigen interference in a vaccine containing rNDVs expressing Env and Gag proteins.

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Section: Increase Cd4mentioning

confidence: 79%

Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus

Khattar

Palaniyandi

Samal

et al. 2015

Human Vaccines & Immunotherapeutics

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“…2,32 We believe the present data are not definitive on this issue, because the formation of the gp120-GRFT complex may eliminate at least some of the possible immunosuppressive effects of gp120, notably those mediated by its mannose moieties. Differently designed studies would be required to answer this point.…”

mentioning

confidence: 73%

Occluding the Mannose Moieties on Human Immunodeficiency Virus Type 1 gp120 with Griffithsin Improves the Antibody Responses to Both Proteins in Mice

Banerjee

Michael

Eggink

et al. 2012

AIDS Research and Human Retroviruses

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To assess the influence of mannosylated glycans on the immunogenicity of human immunodeficiency virus type 1 (HIV-1) Env proteins, we immunized mice with monomeric gp120 in the presence and absence of the mannosebinding protein, griffithsin (GRFT). For comparison, other groups of mice received the nonglycosylated HIV-1 Gag protein, with and without GRFT. Coimmunization with GRFT increased the anti-gp120 IgG reactivity significantly, but had no effect on the anti-Gag response. We also investigated the IgG response to GRFT and found that gp120, but not Gag, enhanced its immunogenicity. For both proteins, IgG1 antibodies dominated the IgG response, with IgG2b as the next most prevalent subclass. We conclude that gp120-GRFT complexes are more immunogenic than the free proteins, for both components, and that occluding the mannose moieties on monomeric gp120 can improve the humoral immune response to this protein.

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“…A recent study by Toapanta et al reported that HIV-1 gp120 interferes with HIV-1 Gag immunogenicity in plasmidimmunized mice. However, this effect of gp120 was observed only with HIV-1 Gag and not with other antigens, and no correlation was found with the level of antigen expression (27). We believe that this inconsistency could be related to the different analysis tools and methods used to track antigen expression and quantify immune responses in the respective studies.…”

Section: Discussionmentioning

confidence: 94%

“…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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Reduction of Anti-HIV-1 Gag Immune Responses During Co-Immunization: Immune Interference by the HIV-1 Envelope

Cited by 27 publications

References 84 publications

Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus

Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus

Occluding the Mannose Moieties on Human Immunodeficiency Virus Type 1 gp120 with Griffithsin Improves the Antibody Responses to Both Proteins in Mice

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

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