Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIV mac251 acquisition in macaques.

Autor:	Rahman MA; Animal Models and Retroviral Vaccines Section, National Cancer Institute, NIH Bethesda, MD, United States., Becerra-Flores M; NYU Langone Health, New York University School of Medicine, New York, NY, United States., Patskovsky Y; NYU Langone Health, New York University School of Medicine, New York, NY, United States., Silva de Castro I; Animal Models and Retroviral Vaccines Section, National Cancer Institute, NIH Bethesda, MD, United States., Bissa M; Animal Models and Retroviral Vaccines Section, National Cancer Institute, NIH Bethesda, MD, United States., Basu S; United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States., Shen X; Department of Surgery, Duke University School of Medicine, Durham, NC, United States., Williams LD; Department of Surgery, Duke University School of Medicine, Durham, NC, United States.; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States., Sarkis S; Animal Models and Retroviral Vaccines Section, National Cancer Institute, NIH Bethesda, MD, United States., N'guessan KF; United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States., LaBranche C; Department of Surgery, Duke University School of Medicine, Durham, NC, United States., Tomaras GD; Department of Surgery, Duke University School of Medicine, Durham, NC, United States.; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States., Aye PP; Veterinary Medicine, Tulane National Primate Research Center, Covington, LA, United States., Veazey R; Division of Comparative Pathology, Department of Pathology and Laboratory Medicine, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA, United States., Paquin-Proulx D; United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States., Rao M; United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States., Franchini G; Animal Models and Retroviral Vaccines Section, National Cancer Institute, NIH Bethesda, MD, United States., Cardozo T; NYU Langone Health, New York University School of Medicine, New York, NY, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Apr 21; Vol. 14, pp. 1139402. Date of Electronic Publication: 2023 Apr 21 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1139402
Abstrakt:	Introduction: An efficacious HIV vaccine will need to elicit a complex package of innate, humoral, and cellular immune responses. This complex package of responses to vaccine candidates has been studied and yielded important results, yet it has been a recurring challenge to determine the magnitude and protective effect of specific in vivo immune responses in isolation. We therefore designed a single, viral-spike-apical, epitope-focused V2 loop immunogen to reveal individual vaccine-elicited immune factors that contribute to protection against HIV/SIV. Method: We generated a novel vaccine by incorporating the V2 loop B-cell epitope in the cholera toxin B (CTB) scaffold and compared two new immunization regimens to a historically protective 'standard' vaccine regimen (SVR) consisting of 2xDNA prime boosted with 2xALVAC-SIV and 1xΔV1gp120. We immunized a cohort of macaques with 5xCTB-V2c vaccine+alum intramuscularly simultaneously with topical intrarectal vaccination of CTB-V2c vaccine without alum (5xCTB-V2/alum). In a second group, we tested a modified version of the SVR consisting of 2xDNA prime and boosted with 1xALVAC-SIV and 2xALVAC-SIV+CTB-V2/alum, (DA/CTB-V2c/alum). Results: In the absence of any other anti-viral antibodies, V2c epitope was highly immunogenic when incorporated in the CTB scaffold and generated highly functional anti-V2c antibodies in the vaccinated animals. 5xCTB-V2c/alum vaccination mediated non-neutralizing ADCC activity and efferocytosis, but produced low avidity, trogocytosis, and no neutralization of tier 1 virus. Furthermore, DA/CTB-V2c/alum vaccination also generated lower total ADCC activity, avidity, and neutralization compared to the SVR. These data suggest that the ΔV1gp120 boost in the SVR yielded more favorable immune responses than its CTB-V2c counterpart. Vaccination with the SVR generates CCR5 - α4β7 + CD4 + Th1, Th2, and Th17 cells, which are less likely to be infected by SIV/HIV and likely contributed to the protection afforded in this regimen. The 5xCTB-V2c/alum regimen likewise elicited higher circulating CCR5 - α4β7 + CD4 + T cells and mucosal α4β7 + CD4 + T cells compared to the DA/CTB-V2c/alum regimen, whereas the first cell type was associated with reduced risk of viral acquisition. Conclusion: Taken together, these data suggest that individual viral spike B-cell epitopes can be highly immunogenic and functional as isolated immunogens, although they might not be sufficient on their own to provide full protection against HIV/SIV infection. Competing Interests: Authors SB, KN’G, and DP-P were employed by Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. Patent applications have been filed with the US Patent and Trademark Office on the use of CTB-V2 immunogens for an HIV vaccine, naming TC and GF as inventors. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Rahman, Becerra-Flores, Patskovsky, Silva de Castro, Bissa, Basu, Shen, Williams, Sarkis, N’guessan, LaBranche, Tomaras, Aye, Veazey, Paquin-Proulx, Rao, Franchini and Cardozo.)
Databáze:	MEDLINE
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