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Viruslike particle vaccine induces protection against respiratory syncytial virus infection in mice.

ABSTRACT: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral death in infants. Despite decades of research with traditional or subunit vaccine approaches, there are no approved RSV vaccines. New approaches are therefore urgently needed to develop effective RSV vaccines.We developed viruslike particles (VLPs) consisting of an influenza virus matrix (M1) protein core and RSV-F or -G on the surface. We tested the immunogenicity and vaccine efficacy of these VLPs (RSV-F, RSV-G) in a mouse model.Intramuscular vaccination with RSV-F or RSV-G VLPs elicited IgG2a dominant RSV-specific immunoglobulin G (IgG) antibody responses against RSV-A2 viruses in both serum and lung extract. Mice immunized with VLPs (RSV-F or RSV-G) showed higher viral neutralizing antibodies in vitro and significantly decreased lung virus loads in vivo after live RSV-A2 challenge. RSV-G VLPs showed better protective efficacy than RSV-F VLPs as determined by the levels of lung virus loads and morbidity postchallenge.This study demonstrates that VLP vaccination provides effective protection against RSV infection. VLPs containing RSV-F and/or RSV-G are potential vaccine candidates against RSV.

SUBMITTER: Quan FS

PROVIDER: S-EPMC3164432 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Viruslike particle vaccine induces protection against respiratory syncytial virus infection in mice.

Quan Fu-Shi FS Kim Yonghwan Y Lee Sujin S Yi Hong H Kang Sang-Moo SM Bozja Jadranka J Moore Martin L ML Compans Richard W RW

The Journal of infectious diseases 20111001 7

<h4>Background</h4>Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral death in infants. Despite decades of research with traditional or subunit vaccine approaches, there are no approved RSV vaccines. New approaches are therefore urgently needed to develop effective RSV vaccines.<h4>Methods</h4>We developed viruslike particles (VLPs) consisting of an influenza virus matrix (M1) protein core and RSV-F or -G on the surface. We tested the immunogenicity and vaccine eff ...[more]

PMID: 21881112

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Project description:Despite the use of vaccines, seasonal influenza remains a risk to public health. We previously proposed the inactivated whole virus particle vaccine (WPV) as an alternative to the widely used split vaccine (SV) for the control of seasonal and pandemic influenza based on the superior priming potency of WPV to that of SV. In this study, we further examined and compared the immunological potency of monovalent WPV and SV of A/California/7/2009 (X-179A) (H1N1) pdm09 (CA/09) to generate immune responses against heterologous viruses, A/Singapore/GP1908/2015 (IVR-180) (H1N1) pdm09 (SG/15), and A/duck/Hokkaido/Vac-3/2007 (H5N1) (DH/07) in mice. Following challenge with a lethal dose of heterologous SG/15, lower virus titer in the lungs and milder weight loss were observed in WPV-vaccinated mice than in SV-vaccinated ones. To investigate the factors responsible for the differences in the protective effect against SG/15, the sera of vaccinated mice were analyzed by hemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) assays to evaluate the antibodies induced against viral hemagglutinin (HA) and neuraminidase (NA), respectively. While the two vaccines induced similar levels of HI antibodies against SG/15 after the second vaccination, only WPV-vaccinated mice induced significantly higher titers of NI antibodies against the strain. Furthermore, given the significant elevation of NI antibody titers against DH/07, an H5N1 avian influenza virus, WPV was also demonstrated to induce NA-inhibiting antibodies that recognize NA of divergent strains. This could be explained by the higher conservation of epitopes of NA among strains than for HA. Taking these findings together, NA-specific antibodies induced by WPV may have contributed to better protection from infection with heterologous influenza virus SG/15, compared with SV. The present results indicate that WPV is an effective vaccine for inducing antibodies against both HA and NA of heterologous viruses and may be a useful vaccine to conquer vaccine strain mismatch.

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Viruslike particle vaccine induces protection against respiratory syncytial virus infection in mice.

Publications

Viruslike particle vaccine induces protection against respiratory syncytial virus infection in mice.

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