Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C

Gómez, Carmen Elena; Nájera, José Luis; Jiménez, Victoria; Bieler, Kurt; Wild, Jens; Kostic, Linda; Heidari, Shirin; Chen, Margaret; Frachette, Marie-Joelle; Pantaleo, Giuseppe; Wolf, Hans; Liljeström, Peter; Wagner, Ralf; Esteban, Mariano

doi:10.1016/j.vaccine.2006.11.051

Cited by 73 publications

(104 citation statements)

References 57 publications

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“…However, Western blot analysis of MVA-and NYVAC-infected chicken embryo fibroblasts showed similar levels of expression of both Env protein and the polyprotein Gag-Pol-Nef. When the immunogenicity of these vaccine vectors was evaluated in HLA-A2 class I transgenic mice, a similar Env immunodominant response was observed (33). Factors such as MHC binding affinity, the efficiency of epitope processing, and competition between T cells for access to antigen-presenting cells could contribute to the observed immunodominant response (32,73,81).…”

Section: Discussionmentioning

confidence: 73%

“…SIV mac239 pcDNA-gag-pol-nef and SHIV 89.6P pcDNA-env (KB9 molecular clone; 47) constructs were made and provided by R. Wagner (University of Regensburg, Germany). The techniques used for the construction of synthetic polygenes were similar to those that were used for preparing the pcDNA-gag-pol-nef of HIV-1 IIIB (20) and pcDNA-env of Chinese clade C HIV-1 strain CN54 (88), as described elsewhere (33).…”

Section: Methodsmentioning

confidence: 99%

“…Both the NYVAC (94) and MVA vectors expressing SIV mac239 gag-pol-nef and SHIV 89.6P env were constructed as described elsewhere (32,33) by using the DNA plasmids described above that were provided by R. Wagner and the pLZAW1 cloning vector that was provided by Sanofi-Pasteur. The resulting plasmids direct the insertion of the foreign genes into the thymidine kinase locus of the MVA and NYVAC genomes, allowing the construction of recombinant viruses lacking a selectable marker.…”

Section: Methodsmentioning

confidence: 99%

“…Although IL-12␤, IFN-␤, and TNF-␣ were upregulated by both vectors, they were increased to higher levels by MVA than by NYVAC. In mice, a comparison of the immune responses revealed a greater magnitude of T-cell responses to HIV-1 inserts expressed by MVA than those expressed by NYVAC (33). However, differences in polyfunctional T-cell subsets have not been explored in either human or nonhuman primates.…”

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confidence: 99%

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Differential CD4⁺versus CD8⁺T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

Mooij

Balla-Jhagjhoorsingh

Koopman

et al. 2008

J Virol

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Poxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in the gene expression of human dendritic cells infected with two leading poxvirus-based human immunodeficiency virus (HIV) vaccine candidates, New York vaccinia virus (NYVAC) and modified vaccinia virus Ankara (MVA). To understand how complex genomic changes in these two vaccine vectors translate into antigen-specific systemic immune responses, we undertook a head-to-head vaccine immunogenicity and efficacy study in the pathogenic HIV type 1 (HIV-1) model of AIDS in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by enzymelinked immunospot assays, but differences were distinguished by multiparameter fluorescence-activated cell sorter analysis, revealing a difference between the number of animals with both CD4 ؉ and CD8 ؉ T-cell responses to vaccine inserts (MVA) and those that elicit a dominant CD4 ؉ T-cell response (NYVAC). Remarkably, vector-induced differences in CD4 ؉ /CD8 ؉ T-cell immune responses persisted for more than a year after challenge and even accompanied antigenic modulation throughout the control of chronic infection. Importantly, strong preexposure HIV-1/simian immunodeficiency virus-specific CD4 ؉ T-cell responses did not prove deleterious with respect to accelerated disease progression. In contrast, in this setting, animals with strong vaccine-induced polyfunctional CD4 ؉ T-cell responses showed efficacies similar to those with stronger CD8 ؉ T-cell responses.

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Section: Discussionmentioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Differential CD4⁺versus CD8⁺T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

Mooij

Balla-Jhagjhoorsingh

Koopman

et al. 2008

J Virol

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“…DNA-C and NYVAC-C prophylactic HIV Clade C vaccines were developed within the EuroVacc vaccine initiative. The insert immunogens have been previously described (11,30). MVA-HPV was kindly provided by Transgene (31).…”

Section: Methodsmentioning

confidence: 99%

Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic

Corbett

Bogers

Heeney

et al. 2008

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

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Each year, approximately five million people die worldwide from putatively vaccine-preventable mucosally transmitted diseases. With respect to mass vaccination campaigns, one strategy to cope with this formidable challenge is aerosol vaccine delivery, which offers potential safety, logistical, and cost-saving advantages over traditional vaccination routes. Additionally, aerosol vaccination may elicit pivotal mucosal immune responses that could contain or eliminate mucosally transmitted pathogens in a preventative or therapeutic vaccine context. In this current preclinical non-human primate investigation, we demonstrate the feasibility of aerosol vaccination with the recombinant poxvirus-based vaccine vectors NYVAC and MVA. Real-time in vivo scintigraphy experiments with radiolabeled, aerosol-administered NYVAC-C (Clade C, HIV-1 vaccine) and MVA-HPV vaccines revealed consistent mucosal delivery to the respiratory tract. Furthermore, aerosol delivery of the vaccines was safe, inducing no vaccine-associated pathology, in particular in the brain and lungs, and was immunogenic. Administration of a DNA-C/NYVAC-C prime/boost regime resulted in both systemic and anal-genital HIV-specific immune responses that were still detectable 5 months after immunization. Thus, aerosol vaccination with NYVAC and MVA vectored vaccines constitutes a tool for large-scale vaccine efforts against mucosally transmitted pathogens.MVA HPV ͉ non-human primate ͉ NYVAC HIV ͉ preclinical study ͉ aerosol vaccine assessment

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Vaccine Analysis: Strategies, Principles, and Control

Nunnally¹,

Turula²,

Sitrin³

2015

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Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C

Cited by 73 publications

References 57 publications

Differential CD4⁺versus CD8⁺T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

Differential CD4⁺versus CD8⁺T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic

Vaccine Analysis: Strategies, Principles, and Control

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Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C

Cited by 73 publications

References 57 publications

Differential CD4+versus CD8+T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

Differential CD4+versus CD8+T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic

Vaccine Analysis: Strategies, Principles, and Control

Contact Info

Product

Resources

About

Differential CD4⁺versus CD8⁺T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

Differential CD4⁺versus CD8⁺T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates