Inactivated vaccine with adjuvants consisting of pattern recognition receptor agonists confers protection against avian influenza viruses in chickens

Tang, Yinghua; Lu, Jihu; Wu, Peipei; Liu, Zhenxing; Tian, Zhen; Zha, Guofei; Chen, Hui; Wang, Qiaochu; Wang, Qiaoxiu; Hou, Fengxiang; Kang, Sang‐Moo; Hou, Jingbo

doi:10.1016/j.vetmic.2014.05.007

Cited by 18 publications

(30 citation statements)

References 27 publications

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“…In the efficacy study, we have detected that the monovalent vaccine combination use with CVCVA5, up regulation of IFNγ and IL-4 levels in serum, and mucosal antibodies in tears and BAL, which are also consistent with our previous study with H5 or H9 vaccine mixing use with CVCVA5 (Tang et al, 2014;Lu et al, 2016). Rising cytokine levels and mucosal immunity may provide some clues to the CVCCVA5 improving the efficacy of vaccine, including vaccine-or antigen-sparing tests, and the sterile immunity test with ND and IBD vaccination.…”

Section: Discussionsupporting

confidence: 90%

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

Feng

et al. 2017

Front. Microbiol.

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We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese. In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines. The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum. Vaccines included the univalent vaccine of Newcastle Disease virus (ND), Egg Drop Syndrome virus (EDS), Infectious Bronchitis virus (IB), and Infectious Bursal Disease virus (IBD). The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage. The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively. The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD. The CVCVA5 also boosted the immune efficacy of the tetravalent vaccine (ND-IB-EDS-H9). A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines. The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals. The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines. Results indicated that the CVCVA5 improved the serum and mucosal antibody levels, cytokine levels of the chickens given the univalent vaccine, and also improved serum antibody titers in bivalent and tetravalent vaccines. This has a potential as an improve vaccine.

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Section: Discussionsupporting

confidence: 90%

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

Feng

et al. 2017

Front. Microbiol.

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“…However, routinely prepared live attenuated-and inactivated virus-based vaccines need strict biosafety conditions with the requirement of adjuvants for injection, limiting their use for oral immunization and long-term storage. 17,18 On the other hand, since spores can resist heat, bacterial spore-based vaccines have the greatest advantages for long-term usage without losing stability. 19 Moreover, spores themselves can have adjuvant effects; therefore, no adjuvants are required for immunization, making oral immunization feasible.…”

Section: Discussionmentioning

confidence: 99%

Development of a heat-stable and orally delivered recombinant M2e-expressing B. subtilis spore-based influenza vaccine

Zhao

Guo

et al. 2014

Human Vaccines & Immunotherapeutics

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Highly conserved ectodomain of influenza virus M2 protein (M2e) is an important target for the development of universal influenza vaccines. Today, the use of chemical or genetic fusion constructs have been undertaken to overcome the low immunogenicity of M2e in vaccine formulation. However, current M2e vaccines are neither orally delivered nor heat-stable. In this study, we evaluated the immune efficacy of an orally delivered recombinant M2e vaccine containing 3 molcules of M2e consensus sequence of influenza A viruses, termed RSM2e3. To accomplish this, CotB, a spore coat of Bacillus subtilis (B. subtilis), was used as a fusion partner, and heat-stable nonpathogenic B. subtilis spores were used as the carrier. Our results showed that CotB-M2e3 fusion had no effect on spore structure or function in the resultant recombinant RSM2e3 strain and that heterologous influenza virus M2e protein was successfully displayed on the surface of the recombinant RSM2e3 spore. Importantly, recombinant RSM2e3 spores elicited strong and long-term M2e-specific systemic and mucosal immune responses, completely protecting immunized mice from lethal challenge of A/PR/8/34(H1N1) influenza virus. Taken together, our study forms a solid basis for the development of a novel orally delivered and heat-stable influenza vaccine based on B. subtilis spore surface display.

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“…The agonists of the pattern recognition receptors are the critical activators of host innate immunity [ 13 , 14 ]. In particular, those agonists are reported to modulate antibody and T helper lymphocyte responses, which added in some inactivated virus-based vaccines as one of the vaccine components [ 15 , 16 ]. We previously reported that the adjuvant, CVCVA5, can significantly improve the protection of commercial H5 and H9 inactivated vaccine in chickens [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Immunopotentiators Improve the Efficacy of Oil-Emulsion-Inactivated Avian Influenza Vaccine in Chickens, Ducks and Geese

Zhang

et al. 2016

PLoS ONE

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Combination of CVCVA5 adjuvant and commercial avian influenza (AI) vaccine has been previously demonstrated to provide good protection against different AI viruses in chickens. In this study, we further investigated the protective immunity of CVCVA5-adjuvanted oil-emulsion inactivated AI vaccine in chickens, ducks and geese. Compared to the commercial H5 inactivated vaccine, the H5-CVCVA5 vaccine induced significantly higher titers of hemaglutinin inhibitory antibodies in three lines of broiler chickens and ducks, elongated the antibody persistence periods in geese, elevated the levels of cross serum neutralization antibody against different clade and subclade H5 AI viruses in chicken embryos. High levels of mucosal antibody were detected in chickens injected with the H5 or H9-CVCA5 vaccine. Furthermore, cellular immune response was markedly improved in terms of increasing the serum levels of cytokine interferon-γ and interleukine 4, promoting proliferation of splenocytes and upregulating cytotoxicity activity in both H5- and H9-CVCVA5 vaccinated chickens. Together, these results provide evidence that AI vaccines supplemented with CVCVA5 adjuvant is a promising approach for overcoming the limitation of vaccine strain specificity of protection.

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Inactivated vaccine with adjuvants consisting of pattern recognition receptor agonists confers protection against avian influenza viruses in chickens

Cited by 18 publications

References 27 publications

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

Development of a heat-stable and orally delivered recombinant M2e-expressing B. subtilis spore-based influenza vaccine

Immunopotentiators Improve the Efficacy of Oil-Emulsion-Inactivated Avian Influenza Vaccine in Chickens, Ducks and Geese

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