HIV-1 vaccines

Excler, Jean–Louis; Robb, Merlin L.; Kim, Jerome H.

doi:10.4161/hv.28462

Cited by 29 publications

(8 citation statements)

References 146 publications

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“…[1][2][3] While the interest in NAb is clear, it should be stressed that RV144 was the only vaccine efficacy trial showing protection against HIV acquisition with little NAb activity but with new patterns of non-NAbs that may block transmission. [4][5][6] Similarly, V2 antibodies seem important for protection against SIV and SHIV challenges. 7 Although this study did not measure non-NAbs, in particular V1 and V2 identified as inversely correlated with risk of acquisition in RV144, this issue should be noted as deserving further studies.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…An efficacious HIV vaccine will be required to induce strong and broad antibody and T cell responses [ 1 ]. To date, such responses have been difficult to obtain using single vaccine modalities, and attempts have been made to improve the immune response with heterologous prime-boost combinations, i.e.…”

Section: Introductionmentioning

confidence: 99%

Alphavirus Replicon DNA Expressing HIV Antigens Is an Excellent Prime for Boosting with Recombinant Modified Vaccinia Ankara (MVA) or with HIV gp140 Protein Antigen

et al. 2015

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Vaccination with DNA is an attractive strategy for induction of pathogen-specific T cells and antibodies. Studies in humans have shown that DNA vaccines are safe, but their immunogenicity needs further improvement. As a step towards this goal, we have previously demonstrated that immunogenicity is increased with the use of an alphavirus DNA-launched replicon (DREP) vector compared to conventional DNA vaccines. In this study, we investigated the effect of varying the dose and number of administrations of DREP when given as a prime prior to a heterologous boost with poxvirus vector (MVA) and/or HIV gp140 protein formulated in glucopyranosyl lipid A (GLA-AF) adjuvant. The DREP and MVA vaccine constructs encoded Env and a Gag-Pol-Nef fusion protein from HIV clade C. One to three administrations of 0.2 μg DREP induced lower HIV-specific T cell and IgG responses than the equivalent number of immunizations with 10 μg DREP. However, the two doses were equally efficient as a priming component in a heterologous prime-boost regimen. The magnitude of immune responses depended on the number of priming immunizations rather than the dose. A single low dose of DREP prior to a heterologous boost resulted in greatly increased immune responses compared to MVA or protein antigen alone, demonstrating that a mere 0.2 μg DREP was sufficient for priming immune responses. Following a DREP prime, T cell responses were expanded greatly by an MVA boost, and IgG responses were also expanded when boosted with protein antigen. When MVA and protein were administered simultaneously following multiple DREP primes, responses were slightly compromised compared to administering them sequentially. In conclusion, we have demonstrated efficient priming of HIV-specific T cell and IgG responses with a low dose of DREP, and shown that the priming effect depends on number of primes administered rather than dose.

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“…A highly successful preventative HIV vaccine will likely require antibodies that neutralize HIV and block virus acquisition. One of the greatest challenges to HIV vaccine development is the elicitation of antibodies with sufficient breadth and potency to counter the genetic diversity of strains that may establish an infection 1 2 . Over the past several years, the cloning and characterization of a number of broadly neutralizing monoclonal antibodies (bNAbs) from HIV-infected humans has identified distinct sites on the HIV Envelope (Env) that are vulnerable to neutralization, and defined several characteristics critical for their protective function 3 4 .…”

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confidence: 99%

Analysis of immunoglobulin transcripts and hypermutation following SHIVAD8 infection and protein-plus-adjuvant immunization

Francica

Sheng

Zhang³

et al. 2015

Nat Commun

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Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIVAD8 infection and Env protein vaccination with eight different adjuvants. A subset of the SHIVAD8-infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies.

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HIV-1 vaccines

Cited by 29 publications

References 146 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

Alphavirus Replicon DNA Expressing HIV Antigens Is an Excellent Prime for Boosting with Recombinant Modified Vaccinia Ankara (MVA) or with HIV gp140 Protein Antigen

Analysis of immunoglobulin transcripts and hypermutation following SHIVAD8 infection and protein-plus-adjuvant immunization

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