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Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center.

ABSTRACT: The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed that a vector-prime protein boost combined vaccine strategy was better than when used alone. Here we have studied three different priming vectors-plasmid DNA, recombinant MVA, and recombinant VSV, all encoding clade C transmitted/founder Env 1086?C gp140, for priming three groups of six non-human primates each, followed by a protein boost with adjuvanted 1086?C gp120 protein. Our data showed that MVA-priming favors the development of higher antibody binding titers and neutralizing activity compared with other vectors. Analyses of the draining lymph nodes revealed that MVA-prime induced increased germinal center reactivity characterized by higher frequencies of germinal center (PNA^hi) B cells, higher frequencies of antigen-specific B-cell responses as well as an increased frequency of the highly differentiated (ICOS^hiCD150^lo) Tfh-cell subset.

SUBMITTER: Eslamizar L

PROVIDER: S-EPMC7835239 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center.

Eslamizar Leila L Petrovas Constantinos C Leggat David J DJ Furr Kathryn K Lifton Michelle L ML Levine Gail G Ma Steven S Fletez-Brant Christopher C Hoyland Wesley W Prabhakaran Madhu M Narpala Sandeep S Boswell Kristin K Yamamoto Takuya T Liao Hua-Xin HX Pickup David D Ramsburg Elizabeth E Sutherland Laura L McDermott Adrian A Roederer Mario M Montefiori David D Koup Richard A RA Haynes Barton F BF Letvin Norman L NL Santra Sampa S

NPJ vaccines 20210125 1

The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed that a vector-prime protein boost combined vaccine strategy was better than when used alone. Here we have studied three different priming vectors-plasmid DNA, recombinant MVA, and recombinant VSV, all encoding clade C transmitted/founder Env 1086 ...[more]

PMID: 33495459

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Project description:Despite the recent progress in the development of new antiviral agents, hepatitis C virus (HCV) infection remains a major global health problem, and there is a need for a preventive vaccine. We previously reported that adenoviral vectors expressing HCV nonstructural proteins elicit protective T cell responses in chimpanzees and were immunogenic in healthy volunteers. Furthermore, recombinant HCV E1E2 protein formulated with adjuvant MF59 induced protective antibody responses in chimpanzees and was immunogenic in humans. To develop an HCV vaccine capable of inducing both T cell and antibody responses, we constructed adenoviral vectors expressing full-length and truncated E1E2 envelope glycoproteins from HCV genotype 1b. Heterologous prime-boost immunization regimens with adenovirus and recombinant E1E2 glycoprotein (genotype 1a) plus MF59 were evaluated in mice and guinea pigs. Adenovirus prime and protein boost induced broad HCV-specific CD8+ and CD4+ T cell responses and functional Th1-type IgG responses. Immune sera neutralized luciferase reporter pseudoparticles expressing HCV envelope glycoproteins (HCVpp) and a diverse panel of recombinant cell culture-derived HCV (HCVcc) strains and limited cell-to-cell HCV transmission. This study demonstrated that combining adenovirus vector with protein antigen can induce strong antibody and T cell responses that surpass immune responses achieved by either vaccine alone.HCV infection is a major health problem. Despite the availability of new directly acting antiviral agents for treating chronic infection, an affordable preventive vaccine provides the best long-term goal for controlling the global epidemic. This report describes a new anti-HCV vaccine targeting the envelope viral proteins based on adenovirus vector and protein in adjuvant. Rodents primed with the adenovirus vaccine and boosted with the adjuvanted protein developed cross-neutralizing antibodies and potent T cell responses that surpassed immune responses achieved with either vaccine component alone. If combined with the adenovirus vaccine targeting the HCV NS antigens now under clinical testing, this new vaccine might lead to a stronger and broader immune response and to a more effective vaccine to prevent HCV infection. Importantly, the described approach represents a valuable strategy for other infectious diseases in which both T and B cell responses are essential for protection.

Dataset Information

Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center.

Publications

Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center.

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