Dataset Information

Comparison of the Immunogenicity of HIV-1 CRF07_BC Gag Antigen With or Without a Seven Amino Acid Deletion in p6 Region.

ABSTRACT: HIV-1 CRF07_BC-p6Δ7, a strain with a seven amino acid deletion in the p6 region of the Gag protein, is becoming the dominant strain of HIV transmission among men who have sex with men (MSM) in China. Previous studies demonstrated that HIV-1 patients infected by CRF07_BC-p6Δ7 strain had lower viral load and slower disease progression than those patients infected with CRF07_BC wild-type strain. However, the underlying mechanism for this observation is not fully clarified yet. In this study, we constructed the recombinant DNA plasmid and adenovirus type 2 (Ad2) vector-based constructs to express the HIV-1 CRF07_BC Gag antigen with or without p6Δ7 mutation and then investigated their immunogenicity in mice. Our results showed that HIV-1 CRF07_BC Gag antigen with p6Δ7 mutation induced a comparable level of Gag-specific antibodies but stronger CD4⁺ and CD8⁺ T-cell immune responses than that of CRF07_BC Gag (07_BC-wt). Furthermore, we identified a series of T-cell epitopes, which induced strong T-cell immune response and cross-immunity with CRF01_AE Gag. These findings implied that the p6^Gag protein with a seven amino acid deletion might enhance the Gag immunogenicity in particular cellular immunity, which provides valuable information to clarify the pathogenic mechanism of HIV-1 CRF07_BC-p6Δ7 and to develop precise vaccine strategies against HIV-1 infection.

SUBMITTER: Li M

PROVIDER: S-EPMC9017423 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Comparison of the Immunogenicity of HIV-1 CRF07_BC Gag Antigen With or Without a Seven Amino Acid Deletion in p6 Region.

Li Minchao M Yuan Yue Y Li Pingchao P Deng Zhaomin Z Wen Ziyu Z Wang Haiying H Feng Fengling F Zou Huachun H Chen Ling L Tang Shixing S Sun Caijun C

Frontiers in immunology 20220405

HIV-1 CRF07_BC-p6Δ7, a strain with a seven amino acid deletion in the p6 region of the Gag protein, is becoming the dominant strain of HIV transmission among men who have sex with men (MSM) in China. Previous studies demonstrated that HIV-1 patients infected by CRF07_BC-p6Δ7 strain had lower viral load and slower disease progression than those patients infected with CRF07_BC wild-type strain. However, the underlying mechanism for this observation is not fully clarified yet. In this study, we con ...[more]

PMID: 35450078

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Project description:An effective vaccine remains the best solution to stop the spread of human immunodeficiency virus (HIV). Cellular immune responses have been repeatedly associated with control of viral replication and thus may be an important element of the immune response that must be evoked by an efficacious vaccine. Recombinant viral vectors can induce potent T-cell responses. Although several viral vectors have been developed to deliver HIV genes, only a few have been advanced for clinical trials. The live-attenuated yellow fever vaccine virus 17D (YF17D) has many properties that make it an attractive vector for AIDS vaccine regimens. YF17D is well tolerated in humans and vaccination induces robust T-cell responses that persist for years. Additionally, methods to manipulate the YF17D genome have been established, enabling the generation of recombinant (r)YF17D vectors carrying genes from unrelated pathogens. Here, we report the generation of seven new rYF17D viruses expressing fragments of simian immunodeficiency virus (SIV)mac239 Gag, Nef, and Vif. Studies in Indian rhesus macaques demonstrated that these live-attenuated vectors replicated in vivo, but only elicited low levels of SIV-specific cellular responses. Boosting with recombinant Adenovirus type-5 (rAd5) vectors resulted in robust expansion of SIV-specific CD8(+) T-cell responses, particularly those targeting Vif. Priming with rYF17D also increased the frequency of CD4(+) cellular responses in rYF17D/rAd5-immunized macaques compared to animals that received rAd5 only. The effect of the rYF17D prime on the breadth of SIV-specific T-cell responses was limited and we also found evidence that some rYF17D vectors were more effective than others at priming SIV-specific T-cell responses. Together, our data suggest that YF17D - a clinically relevant vaccine vector - can be used to prime AIDS virus-specific T-cell responses in heterologous prime boost regimens. However, it will be important to optimize rYF17D-based vaccine regimens to ensure maximum delivery of all immunogens in a multivalent vaccine.

Dataset Information

Comparison of the Immunogenicity of HIV-1 CRF07_BC Gag Antigen With or Without a Seven Amino Acid Deletion in p6 Region.

Publications

Comparison of the Immunogenicity of HIV-1 CRF07_BC Gag Antigen With or Without a Seven Amino Acid Deletion in p6 Region.

Similar Datasets

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