Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

Hb, Wang; Kondo, Asami; Yoshida, Atsushi; Yoshizaki, Shinji; S, Abe; Ll, Bao; Mizuki, Nobuhisa; Ichino, Motohide; Klinman, Dennis M.; Okuda, Kenji; Shimada, Masaru

doi:10.1038/gt.2009.122

Cited by 18 publications

(7 citation statements)

References 56 publications

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“…Along the same line, various vaccine strategies have been proposed to help restimulate HIV-specific immunity allowing HIV-infected patients to reduce time on antiretroviral therapy (ART) [7,8]. Various therapeutic vaccine candidates including peptide-, protein-, and viral vector-based vaccines have shown modest efficacy in experimental animal models [9,10] and patients [11][12][13][14][15][16][17][18]. Some candidate vaccines, such as ALVAC or Ad5, have induced potent increase in HIV-specific immune responses [19,20].…”

Section: Introductionmentioning

confidence: 99%

NYVAC immunization induces polyfunctional HIV‐specific T‐cell responses in chronically‐infected, ART‐treated HIV patients

et al. 2012

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We report the results of the Theravac-01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus-based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC-B vaccine was injected intramuscularly into ten HIV-infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV-specific T-cell responses following immunization were quantitatively analyzed using an IFN-γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC-B vaccine is safe and highly immunogenic, as indicated by increased HIV-specific T-cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T-cell responses, and the appearance of newly detected HIV-specific CD4 + and CD8 + T-cell responses were observed. Furthermore, immunization mostly induced an increase in Gag-specific T-cell responses. In conclusion, NYVAC-B immunization induces broad, vigorous, and polyfunctional HIV-specific T-cell responses, suggesting that poxvirus-based vaccine regimens may be instrumental in the therapeutic HIV vaccine field. Eur. J. Immunol. 2012. 42: 3038-3048 Clinical immunology 3039 IntroductionThe development of antiviral therapy has dramatically changed the course and the prognosis of HIV infection. More than 30 antiviral drugs available offer many therapeutic options for the patients and some of these drugs used in combination are able to induce long-term suppression of virus replication as indicated by the persistence of levels of viremia below the limit of detection of highly sensitive PCR assays [1]. The antiviral therapy-mediated suppression of virus replication has resulted in dramatic reduction of morbidity and mortality, and HIV infection has shifted from being a life threatening to a chronic viral disease [2]. In this regard, recent studies have estimated a life expectancy of 25-30 years for subjects with HIV infection [3,4]. Despite the long-term suppression of virus replication and the normalization of a series of immunological parameters, which are not limited to the CD4 + T-cell counts but also to the recovery of a series of antigen-specific (including HIV) immunological functions, the interruption of antiviral therapy is almost invariably associated to virus rebound [1,5]. These observations indicated that the long-term suppression of virus replication does not result in the generation of an effective HIV-specific immune response [6].For these reasons, a number of immunological interventions have been investigated in the past and are currently being investigated to stimulate HIV-specific immune responses that may efficiently control HIV replication also in the absence of antiviral therapy. Among these interventions, particular attention has been given to the development of therapeutic v...

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Section: Introductionmentioning

confidence: 99%

NYVAC immunization induces polyfunctional HIV‐specific T‐cell responses in chronically‐infected, ART‐treated HIV patients

et al. 2012

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“…Nevertheless, the virus displayed the cell tropism of Ad35. Using the Ad5/35 vector, we found that high immunogenicity of the vaccine was observed in both mice and non-human primates [39], [40]. Coupled with the evidence that an Ad5/35 vector transduces human dendritic cells more efficiently as compared with an Ad5 vector [41], these findings suggest that the Ad5/35-HIV vector is a promising candidate for human trials.…”

Section: Discussionmentioning

confidence: 69%

Immunogenic Comparison of Chimeric Adenovirus 5/35 Vector Carrying Optimized Human Immunodeficiency Virus Clade C Genes and Various Promoters

et al. 2012

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Adenovirus vector-based vaccine is a promising approach to protect HIV infection. However, a recent phase IIb clinical trial using the vector did not show its protective efficacy against HIV infection. To improve the vaccine, we explored the transgene protein expression and its immunogenicity using optimized codon usage, promoters and adaptors. We compared protein expression and immunogenicity of adenovirus vector vaccines carrying native or codon usage-optimized HIV-1 clade C gag and env genes expression cassettes driven by different promoters (CMV, CMVi, and CA promoters) and adapters (IRES and F2A). The adenovirus vector vaccine containing optimized gag gene produced higher Gag protein expression and induced higher immune responses than the vector containing native gag gene in mice. Furthermore, CA promoter generated higher transgene expression and elicited higher immune responses than other two popularly used promoters (CMV and CMVi). The second gene expression using F2A adaptor resulted in higher protein expression and immunity than that of using IRES and direct fusion protein. Taken together, the adenovirus vector containing the expression cassette with CA promoter, optimized HIV-1 clade C gene and an F2A adaptor produced the best protein expression and elicited the highest transgene-specific immune responses. This finding would be promising for vaccine design and gene therapy.

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“…Previous studies showed that an adenovirus vector (Ad) vaccine against HIV could induce a strong Ag-specific immune response in humans and animal models [12,25,26,31,32]. However the Ad vaccine failed to protect against HIV infection in STEP human clinical trials [12,32].…”

Section: Resultsmentioning

confidence: 99%

Apoptosis of antigen-specific CTLs contributes to low immune response in gut-associated lymphoid tissue post vaccination

Shimada

Yoshizaki

Ichino

et al. 2014

Vaccine

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The gut-associated lymphoid tissue (GALT) represents a major reservoir of HIV in infected individuals. Vaccines can induce strong systemic immune responses but these have less impact on CD4 T cells activity and numbers in GALT. In this study, we vaccinated mice with an adenovirus vector that expressed the envelope gene from HIV and observed immune responses in the peripheral blood, spleen, liver, mesenteric lymph nodes, and Peyer's patches. We found that (1) the number of HIV-specific CD8 T cells was dramatically lower in GALT than in other tissues; (2) the programmed cell death protein-1 (PD-1) was expressed at high levels in HIV-specific CD8 T cells including memory T cells in GALT; and (3) high levels of HIV-specific CD8 T cell apoptosis were occurring in GALT. These results suggest that contributing to GALT becoming an HIV reservoir during infection is a combination of exhaustion and/or dysfunction of HIV-specific CTLs at that site. These results emphasize the importance of developing of an effective mucosal vaccine against HIV.

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Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

Cited by 18 publications

References 56 publications

NYVAC immunization induces polyfunctional HIV‐specific T‐cell responses in chronically‐infected, ART‐treated HIV patients

NYVAC immunization induces polyfunctional HIV‐specific T‐cell responses in chronically‐infected, ART‐treated HIV patients

Immunogenic Comparison of Chimeric Adenovirus 5/35 Vector Carrying Optimized Human Immunodeficiency Virus Clade C Genes and Various Promoters

Apoptosis of antigen-specific CTLs contributes to low immune response in gut-associated lymphoid tissue post vaccination

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