Oral Vaccination Approaches for Anti-SHIV Immunity.

Autor: Velarde de la Cruz E; Department of Medicine, Boston Children's Hospital, Boston, MA, United States.; Department of Pediatrics, Harvard Medical School, Boston, MA, United States., Wang L; Department of Medicine, Boston Children's Hospital, Boston, MA, United States.; Department of Pediatrics, Harvard Medical School, Boston, MA, United States., Bose D; Department of Medicine, Boston Children's Hospital, Boston, MA, United States.; Department of Pediatrics, Harvard Medical School, Boston, MA, United States., Gangadhara S; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States.; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, United States., Wilson RL; Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, United States., Amara RR; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States.; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, United States., Kozlowski PA; Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, United States., Aldovini A; Department of Medicine, Boston Children's Hospital, Boston, MA, United States.; Department of Pediatrics, Harvard Medical School, Boston, MA, United States.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2021 Jun 21; Vol. 12, pp. 702705. Date of Electronic Publication: 2021 Jun 21 (Print Publication: 2021).
DOI: 10.3389/fimmu.2021.702705
Abstrakt: We modified a Sabin Oral Poliovirus Vaccine (OPV) vector to permit secretion of the antigens of interest with the goal of improving anti-HIV Env humoral responses in a SHIV mucosal immunization composed of DNA and recombinant OPVs. We evaluated stimulation of systemic and mucosal cell-mediated and humoral immunity in Rhesus macaques by two regimens, both involving a prime with a SHIV BG505  DNA construct producing non-infectious particles formulated in lipid nanoparticles, administered in the oral cavity, and two different viral vector boostings, administered in the oral cavity and intestinally.   Group 1 was boosted with rMVA-SHIVBG505, expressing SIV Gag/Pol and HIV BG505  Env. Group 2 was boosted with a SHIV BG505 -OPV vaccine including a non-secreting SIV mac239 CA-p6-OPV, expressing Gag CA, NC and p6 proteins, and a HIV BG505 C1-V2-OPV, secreting the C1-V2 fragment of HIV Env BG505 , recognized by the broadly neutralizing antibody PG16. A time course analysis of anti-SHIV Gag and Env CD4+ and CD8+ T-cell responses in PBMC and in lymph node, rectal, and vaginal MNC was carried out. Both regimens stimulated significant cell-mediated responses in all compartments, with SHIV BG505 -OPV immunization stimulating more significant levels of responses than rMVA- SHIV BG505 . Boolean analysis of these responses revealed predominantly monofunctional responses with multifunctional responses also present in all tissues. Stimulation of antibody responses was disappointing in both groups with negative anti-SHIV IgG in plasma, and IgA in salivary, rectal and vaginal secretions being restricted to a few animals. After repeated rectal challenge with SHIV BG505 , two Group 1 animals remained uninfected at challenge termination. No significant differences were observed in post-infection viral loads between groups. After the acute phase decline, CD4+ T cell percentages returned to normal levels in vaccinated as well as control animals. However, when compared to controls, vaccinate groups had more significant preservation of PBMC and rectal MNC Th17/Treg ratios, considered the strongest surrogate marker of progression to AIDS. We conclude that the vaccine platforms used in this study are insufficient to stimulate significant humoral immunity at the tested doses and schedule but sufficient to stimulate significant mucosal and systemic cell-mediated immunity, impacting the preservation of key Th17 CD4+ T cells in blood and rectal mucosa.
Competing Interests: The 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 © 2021 Velarde de la Cruz, Wang, Bose, Gangadhara, Wilson, Amara, Kozlowski and Aldovini.)
Databáze: MEDLINE
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