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Supplementation of inactivated influenza vaccine with norovirus P particle-M2e chimeric vaccine enhances protection against heterologous virus challenge in chickens.

ABSTRACT: The current inactivated influenza vaccines provide satisfactory protection against homologous viruses but limited cross-protection against antigenically divergent strains. Consequently, there is a need to develop more broadly protective vaccines. The highly conserved extracellular domain of the matrix protein 2 (M2e) has shown promising results as one of the components of a universal influenza vaccine in different animal models. As an approach to overcome the limited, strain specific, protective efficacy of inactivated influenza vaccine (IIV), a combination of recombinant M2e expressed on the surface of norovirus P particle (M2eP) and IIV was tested in chickens. Co-immunization of birds with both vaccines did not affect the production of M2e-specific IgG antibodies compared to the group vaccinated with M2eP alone. However, the co-immunized birds developed significantly higher pre-challenge hemagglutination inhibition antibody titers against the homologous IIV antigen and heterologous challenge virus. These combined vaccine groups also had cross reactive antibody responses against different viruses (H5, H6, and H7 subtypes) compared to the IIV alone vaccinated group. Upon intranasal challenge with homologous and heterologous viruses, the combined vaccine groups showed greater reduction in viral shedding in tracheal swabs compared to those groups receiving IIV alone. Moreover, M2eP antisera from vaccinated birds were able to bind to the native M2 expressed on the surface of whole virus particles and infected cells, and inhibit virus replication in vitro. Our results support the potential benefit of supplementing IIV with M2eP, to expand the vaccine cross protective efficacy.

SUBMITTER: Elaish M

PROVIDER: S-EPMC5289506 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Supplementation of inactivated influenza vaccine with norovirus P particle-M2e chimeric vaccine enhances protection against heterologous virus challenge in chickens.

Elaish Mohamed M Ngunjiri John M JM Ali Ahmed A Xia Ming M Ibrahim Mahmoud M Jang Hyesun H Hiremath Jagadish J Dhakal Santosh S Helmy Yosra A YA Jiang Xi X Renukaradhya Gourapura J GJ Lee Chang-Won CW

PloS one 20170202 2

The current inactivated influenza vaccines provide satisfactory protection against homologous viruses but limited cross-protection against antigenically divergent strains. Consequently, there is a need to develop more broadly protective vaccines. The highly conserved extracellular domain of the matrix protein 2 (M2e) has shown promising results as one of the components of a universal influenza vaccine in different animal models. As an approach to overcome the limited, strain specific, protective ...[more]

PMID: 28151964

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Project description:Background: Vaccines may have non-specific effects, affecting resistance to heterologous pathogens. Veterinary vaccines have seldom been investigated for their non-specific effects. However, recent observational studies suggest that an inactivated paratuberculosis vaccine reduced all-cause mortality in goats and cattle. Aim: We tested if vaccination with a killed mycobacterial vaccine may have heterologous effects in swine (Sus domesticus), specifically on the pathogenic and clinical effects of a heterologous challenge with Actinobacillus pleuropneumoniae in young pigs. Methods: Newborn piglets were randomized to vaccination s.c. with the inactivated paratuberculosis vaccine Gudair (Zoetis Inc.) (n = 17) or no vaccine (n = 16). At 4-5 weeks after vaccination, all piglets were challenged intra-nasally with a high (Gudair: n = 8; control: n = 8) or a low (Gudair: n = 9; control: n = 8) dose of the gram-negative bacterium A. pleuropneumoniae causing acute porcine pleuropneumonia. The effect and severity of pathogen challenge was evaluated by measuring acute phase proteins C-reactive protein, haptoglobin and Porcine α1-acid glycoprotein, and by gross pathology 1 day post challenge. Specific and non-specific in vitro cytokine responses to vaccination were evaluated in whole blood before bacterial challenge. Results: The vaccine was immunogenic in the pigs as evidenced by increased IFN-γ responses to purified protein derivative of Mycobacterium paratuberculosis. However, Gudair vaccine did not affect IL-6 responses. The gross pathology of the lungs as well as the acute phase protein responses after the high A. pleuropneumoniae dose challenge was slightly increased in the vaccinated animals compared with controls, whereas this was not seen in the animals receiving the low-dose bacterial challenge. Conclusion: The inactivated paratuberculosis vaccine exacerbated the pathological and inflammatory effects of an experimental A. pleuropneumoniae infection in young pigs.

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.

Dataset Information

Supplementation of inactivated influenza vaccine with norovirus P particle-M2e chimeric vaccine enhances protection against heterologous virus challenge in chickens.

Publications

Supplementation of inactivated influenza vaccine with norovirus P particle-M2e chimeric vaccine enhances protection against heterologous virus challenge in chickens.

Similar Datasets

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