Boost and Increased Antibody Breadth Following a Second Dose of PARVAX for SARS-CoV-2 in Mice and Nonhuman Primates.

Autor:	Bhatt U; Grousbeck Gene Therapy Center, Ocular Genomics Institute and Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.; Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Herate C; Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, 92260 Fontenay-aux-Roses, France., Estelien R; Grousbeck Gene Therapy Center, Ocular Genomics Institute and Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.; Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Relouzat F; Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, 92260 Fontenay-aux-Roses, France., Dereuddre-Bosquet N; Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, 92260 Fontenay-aux-Roses, France., Maciorowski D; Grousbeck Gene Therapy Center, Ocular Genomics Institute and Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.; Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Diop C; Grousbeck Gene Therapy Center, Ocular Genomics Institute and Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.; Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Couto E; Grousbeck Gene Therapy Center, Ocular Genomics Institute and Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.; Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Staiti J; Grousbeck Gene Therapy Center, Ocular Genomics Institute and Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.; Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Cavarelli M; Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, 92260 Fontenay-aux-Roses, France., Bossevot L; Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, 92260 Fontenay-aux-Roses, France., Sconosciuti Q; Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, 92260 Fontenay-aux-Roses, France., Bouchard P; Ciendias Bio, Weston, MA 02493, USA., Le Grand R; Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, 92260 Fontenay-aux-Roses, France., Vandenberghe LH; Grousbeck Gene Therapy Center, Ocular Genomics Institute and Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.; Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.; Ciendias Bio, Weston, MA 02493, USA., Zabaleta N; Grousbeck Gene Therapy Center, Ocular Genomics Institute and Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.; Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Jazyk:	angličtina
Zdroj:	Vaccines [Vaccines (Basel)] 2024 Aug 02; Vol. 12 (8). Date of Electronic Publication: 2024 Aug 02.
DOI:	10.3390/vaccines12080882
Abstrakt:	PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, a low-dose prime followed by a higher-dose boost elicited potent neutralizing antibody responses and distinct cross-reactivity profiles, depending on the antigen used in the booster vaccine. However, the potent neutralizing anti-vector antibody responses developed in mice limited the dose that could be administered as a prime. We further explored the re-administration efficacy in NHPs primed with a SARS-CoV-2 Delta vaccine and boosted with an Omicron BA.1 vaccine at week 15, after the primary response peak antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was detected in the antibody titers for other variants. The anti-vector responses were low and showed some increased subsequent boosts but generally declined over time. The potent prime vaccination limited the detection of the boosting effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data show that PARVAX can be effectively re-administered and induce a novel antigenic response.
Databáze:	MEDLINE
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