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Heterologous MVA-S prime Ad5-S boost regimen induces high and persistent levels of neutralizing antibody response against SARS coronavirus.

ABSTRACT: Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (CoV), SARS-CoV. In previous studies, we showed that a SARS-CoV spike (S) glycoprotein-based modified vaccinia Ankara (MVA-S) vaccine could induce strong neutralizing antibody (Nab) response which might have played a critical role in protecting Chinese rhesus monkeys from the pathogenic viral challenge. To date, however, it remains unknown what the minimal level of Nab is required to achieve sterile immunity in humans. It is therefore important to explore techniques to maximize the level of Nab response in vivo. Here, we evaluate various vaccination regimens using combinations of DNA-S, MVA-S, and adenovirus type 5 (Ad5-S) vaccines. We show that in vaccinated mice and rabbits, a heterologous MVA-S prime with Ad5-S boost regimen induces the highest and most persistent level of Nab response when compared with other combinations. Interestingly, the initial level of Nab after prime does not necessarily predict the magnitude of the secondary response after the boost. Thus, our data provides a promising optimal regimen for vaccine development in humans against SARS-CoV infection.

SUBMITTER: Ba L

PROVIDER: S-EPMC7079952 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Heterologous MVA-S prime Ad5-S boost regimen induces high and persistent levels of neutralizing antibody response against SARS coronavirus.

Ba Lei L Yi Christopher E CE Zhang Linqi L Ho David D DD Chen Zhiwei Z

Applied microbiology and biotechnology 20070621 5

Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (CoV), SARS-CoV. In previous studies, we showed that a SARS-CoV spike (S) glycoprotein-based modified vaccinia Ankara (MVA-S) vaccine could induce strong neutralizing antibody (Nab) response which might have played a critical role in protecting Chinese rhesus monkeys from the pathogenic viral challenge. To date, however, it remains unknown what the minimal level of Nab is required to achieve sterile immunity in humans. It ...[more]

PMID: 17581748

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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.

Project description:BackgroundEmerging evidence suggests heterologous prime-boost COVID-19 vaccination as a superior strategy than homologous schedules. Animal experiments and clinical observations have shown enhanced antibody response against influenza variants after heterologous vaccination; however, whether the inoculation order of COVID-19 vaccines in a prime-boost schedule affects antibody response against SARS-CoV-2 variants is not clear.MethodsWe conducted immunological analyses in a cohort of health care workers (n = 486) recently vaccinated by three types of inactivated COVID-19 vaccines under homologous or heterologous prime-boost schedules. Antibody response against ancestral SARS-CoV-2 (Wuhan-Hu-1) was assessed by total antibody measurements, surrogate virus neutralization tests, and pseudovirus neutralization assays (PNA). Furthermore, serum neutralization activity against SARS-CoV-2 variants of concern was also measured by PNA.FindingsWe observed strongest serum neutralization activity against the widely circulating SARS-CoV-2 variant B.1.617.2 among recipients of heterologous BBIBP-CorV/CoronaVac and WIBP-CorV/CoronaVac. In contrast, recipients of CoronaVac/BBIBP-CorV and CoronaVac/WIBP-CorV showed significantly lower B.1.617.2 neutralization titers than recipients of reverse schedules. Laboratory tests revealed that neutralizing activity against common variants but not the ancestral SARS-CoV-2 was associated with the inoculation order of heterologous prime-boost vaccines. Multivariable regression analyses confirmed this association after adjusting for known confounders.ConclusionsOur data provide clinical evidence of inoculation order-dependent expansion of neutralizing breadth against SARS-CoV-2 in recipients of heterologous prime-boost vaccination and call for further studies into its underlying mechanism.FundingNational Key R&D Program of China, National Development and Re-form Commission of China, National Natural Science Foundation of China, Shenzhen Science and Technology Innovation Commission, and US Department of Veterans Affairs.

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Heterologous MVA-S prime Ad5-S boost regimen induces high and persistent levels of neutralizing antibody response against SARS coronavirus.

Publications

Heterologous MVA-S prime Ad5-S boost regimen induces high and persistent levels of neutralizing antibody response against SARS coronavirus.

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