A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques.

Autor:	Sahoo A; Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA., Jones AT; Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA., Cheedarla N; Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA., Gangadhara S; Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA., Roy V; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Styles TM; Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA., Shiferaw A; Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA., Walter KL; Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA., Williams LD; Department of Surgery, Duke University Medical School, Duke University, Durham, NC 27710, USA., Shen X; Department of Surgery, Duke University Medical School, Duke University, Durham, NC 27710, USA., Ozorowski G; Department of Integrative Structural and Computational Biology, Scripps Research Institute, San Diego, CA 92121, USA., Lee WH; Department of Integrative Structural and Computational Biology, Scripps Research Institute, San Diego, CA 92121, USA., Burton S; Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Yi L; Department of Biochemistry, Emory Glycomics and Molecular Interactions Core (EGMIC), School of Medicine, Emory University, Atlanta, GA 30322, USA., Song X; Department of Biochemistry, Emory Glycomics and Molecular Interactions Core (EGMIC), School of Medicine, Emory University, Atlanta, GA 30322, USA., Qin ZS; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA., Derdeyn CA; Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA., Ward AB; Department of Integrative Structural and Computational Biology, Scripps Research Institute, San Diego, CA 92121, USA., Clements JD; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 8638, USA., Varadarajan R; Molecular Biophysics Unit (MBU), Indian Institute of Science, Bengaluru, Karnataka 560012, India.; Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru, Karnataka 560012, India., Tomaras GD; Department of Surgery, Duke University Medical School, Duke University, Durham, NC 27710, USA., Kozlowski PA; Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA., Alter G; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Amara RR; Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2022 Jul 22; Vol. 7 (73), pp. eabl4102. Date of Electronic Publication: 2022 Jul 22.
DOI:	10.1126/sciimmunol.abl4102
Abstrakt:	The rising global HIV-1 burden urgently requires vaccines capable of providing heterologous protection. Here, we developed a clade C HIV-1 vaccine consisting of priming with modified vaccinia Ankara (MVA) and boosting with cyclically permuted trimeric gp120 (CycP-gp120) protein, delivered either orally using a needle-free injector or through parenteral injection. We tested protective efficacy of the vaccine against intrarectal challenges with a pathogenic heterologous clade C SHIV infection in rhesus macaques. Both routes of vaccination induced a strong envelope-specific IgG in serum and rectal secretions directed against V1V2 scaffolds from a global panel of viruses with polyfunctional activities. Envelope-specific IgG showed lower fucosylation compared with total IgG at baseline, and most of the vaccine-induced proliferating blood CD4 + T cells did not express CCR5 and α4β7, markers associated with HIV target cells. After SHIV challenge, both routes of vaccination conferred significant and equivalent protection, with 40% of animals remaining uninfected at the end of six weekly repeated challenges with an estimated efficacy of 68% per exposure. Induction of envelope-specific IgG correlated positively with G1FB glycosylation, and G2S2F glycosylation correlated negatively with protection. Vaccine-induced TNF-α + IFN-γ + CD8 + T cells and TNF-α + CD4 + T cells expressing low levels of CCR5 in the rectum at prechallenge were associated with decreased risk of SHIV acquisition. These results demonstrate that the clade C MVA/CycP-gp120 vaccine provides heterologous protection against a tier2 SHIV rectal challenge by inducing a polyfunctional antibody response with distinct Fc glycosylation profile, as well as cytotoxic CD8 T cell response and CCR5-negative T helper response in the rectum.
Databáze:	MEDLINE
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