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Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVmac251 acquisition in macaques.
Rahman, Mohammad Arif; Becerra-Flores, Manuel; Patskovsky, Yury; Silva de Castro, Isabela; Bissa, Massimiliano; Basu, Shraddha; Shen, Xiaoying; Williams, LaTonya D; Sarkis, Sarkis; N'guessan, Kombo F; LaBranche, Celia; Tomaras, Georgia D; Aye, Pyone Pyone; Veazey, Ronald; Paquin-Proulx, Dominic; Rao, Mangala; Franchini, Genoveffa; Cardozo, Timothy.
Afiliación
  • 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.
  • Shen X; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States.
  • Williams LD; Department of Surgery, Duke University School of Medicine, Durham, NC, United States.
  • Sarkis S; Department of Surgery, Duke University School of Medicine, Durham, NC, United States.
  • N'guessan KF; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States.
  • LaBranche C; Animal Models and Retroviral Vaccines Section, National Cancer Institute, NIH Bethesda, MD, United States.
  • Tomaras GD; United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
  • Aye PP; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States.
  • Veazey R; Department of Surgery, Duke University School of Medicine, Durham, NC, United States.
  • Paquin-Proulx D; Department of Surgery, Duke University School of Medicine, Durham, NC, United States.
  • Rao M; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States.
  • Franchini G; Veterinary Medicine, Tulane National Primate Research Center, Covington, LA, United States.
  • Cardozo T; Division of Comparative Pathology, Department of Pathology and Laboratory Medicine, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA, United States.
Front Immunol ; 14: 1139402, 2023.
Article en En | MEDLINE | ID: mdl-37153584
ABSTRACT

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- α4ß7+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- α4ß7+ CD4+ T cells and mucosal α4ß7+ 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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Infecciones por VIH / Vacunas contra el SIDA Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Infecciones por VIH / Vacunas contra el SIDA Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos