Intranasal immunization with influenza antigens conjugated with cholera toxin subunit B stimulates broad spectrum immunity against influenza viruses.
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ABSTRACT:
SUBMITTER: Li J
PROVIDER: S-EPMC4896531 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:The development of a universal influenza vaccine is an ideal strategy to eliminate public health threats from influenza epidemics and pandemics. This ultimate goal is restricted by the low immunogenicity of conserved influenza epitopes. Layered protein nanoparticles composed of well-designed conserved influenza structures have shown improved immunogenicity with new physical and biochemical features. Herein, structure-stabilized influenza matrix protein 2 ectodomain (M2e) and M2e-neuraminidase fusion (M2e-NA) recombinant proteins are generated and M2e protein nanoparticles and double-layered M2e-NA protein nanoparticles are produced by ethanol desolvation and chemical crosslinking. Immunizations with these protein nanoparticles induce immune protection against different viruses of homologous and heterosubtypic NA in mice. Double-layered M2e-NA protein nanoparticles induce higher levels of humoral and cellular responses compared with their comprising protein mixture or M2e nanoparticles. Strong cytotoxic T cell responses are induced in the layered M2e-NA protein nanoparticle groups. Antibody responses contribute to the heterosubtypic NA immune protection. The protective immunity is long lasting. These results demonstrate that double-layered protein nanoparticles containing structure-stabilized M2e and NA can be developed into a universal influenza vaccine or a synergistic component of such vaccines. Layered protein nanoparticles can be a general vaccine platform for different pathogens.
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Project description:UnlabelledInfluenza vaccines aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes. We proposed that vaccines targeting both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide protection against infection with the same subtype and also HSI against other subtypes. We report here that single intranasal immunization with a recombinant adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced significant HA- and M2e-specific Ab responses, along with protection against heterosubtypic challenge in mice. The protection is superior compared to that induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While protection against homotypic H5 virus is primarily mediated by virus-neutralizing Abs, the cross-protection is associated with Abs directed to conserved stalk HA and M2e that seem to have an additive effect. Consistently, adoptive transfer of antisera induced by rAdH5/M2e provided the best protection against heterosubtypic challenge compared to that provided by antisera derived from mice immunized with rAdH5 or rAdM2e. These results support the development of rAd-vectored vaccines encoding both H5 and M2e as universal vaccines against different IAV subtypes.ImportanceCurrent licensed influenza vaccines provide protection limited to the infection with same virus strains; therefore, the composition of influenza vaccines has to be revised every year. We have developed a new universal influenza vaccine that is highly efficient in induction of long-lasting cross-protection against different influenza virus strains. The cross-protection is associated with a high level of vaccine-induced antibodies against the conserved stalk domain of influenza virus hemagglutinin and the ectodomain of matrix protein. The vaccine could be used to stimulate cross-protective antibodies for the prevention and treatment of influenza with immediate effect for individuals who fail to respond to or receive the vaccine in due time. The vaccine offers a new tool to control influenza outbreaks, including pandemics.
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Project description:Animals can be rendered immune to Ascaris parasites by immunization with infectious-stage larvae. The specific parasite gene products that mediate protective responses in ascariasis are unknown. We have identified a cDNA encoding Ascaris suum 14-kDa antigen (As14) and evaluated the vaccinal effect of the Escherichia coli-expressed recombinant protein (rAs14). GenBank analysis showed that As14 has low similarity at the amino acid level to a Caenorhabditis elegans gene product and to antigens of the filarial nematodes but not to other known proteins. In addition, As14 homologues were found to be expressed in human and dog roundworms. In mice that received intranasal administration of rAs14 coupled with cholera toxin B subunit (rAs14-CTB), there was a 64% reduction of recovery of larvae compared with that in the nontreated group. The vaccinated mice showed a significant increase in the total serum immunoglobulin G (IgG) levels and the mucosal IgA responses. Elevation of the rAs14-specific IgE response was also seen. Measurement of the IgG subclasses showed a higher level of IgG1 and a lower level of IgG2a antibody response in the sera of the immunized mice, suggesting that protection was associated with a type II immune response. As14 is the first protective antigen against A. suum infection to be identified. Our immunization trial results in laboratory animals suggest the possibility of developing a mucosal vaccine for parasitic diseases caused by ascarid nematodes.
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