Efficacy Of Influenza Vaccine Based On Pre-exposure To Seasonal Influenza

Influenza A is the most recurring respiratory disease in humans. Influenza viruses circulate in humans every year in every part of the world. Intermittently and unpredictably new viruses arise that are capable of causing pandemics. The host responds to the viral infection by generating lifelong memory cells and neutralizing Abs. This generates variant viruses that can no longer be romoved by immune response.This paper consists of five parts:(1) Introduction of influenza virus, influenza vaccines and infection of influenza virus etc. Description of the knowledge includes basic features of influenza virus A, the classification of influenza vaccines and the nonspecific and specific immune responses elicited by infection of influenza virus.(2) Research on protective abilities against homosubtypic influenza virus challenge provided by H5N1NP Ml DNA vaccine after infection of seasonal influenza. Pre-infection elicited immune memory to influenza virus in vivo, which can provide partial protection to mutated influenza virus. In this study, BALB/c mice were infected by A/PR8(H1N1), which elicited homologous immune memory to influenza virus, and then vaccinated by H5N1internal conserved gene NP, M1and NP+M1vaccines respectively. The protective abilities against H5N1influenza virus were compared with those from mice vaccinated by vaccines alone without pre-exposure to A/PR8. Specific IgG antibodies in serum were detected by ELISA, and spleen cells were detected by ELISPOT. The protective efficacy was judged by survival rates, body weight loss and residue virus titer in lungs after challenge. The results indicated that pre-existing immunity plus single dose infection with H5N1NP+M1DNA vaccine could offer mice excellent protection against homotypic influenza.(3) Research on cross-protection against influenza virus challenge provided by H5N1NP M1DNA vaccines with pre-infection of seasonal influenza virus. This study was demonstrated on the basis of former experiment. Mice were infected by A/PR8(H1N1), which elicited immune memory to influenza virus in the body, and vaccinated once with H5N1NP+M1DNA vaccine, and then challenged with a lethal dose of H1N1, H3N2, H9N2and H10N8respectively. Residue virus titer in lung, body weight loss and survival rates were observed. Results showed that DNA vaccination with pre-infection could offer at least80%protection against H9N2and H10N8influenza virus, which were isolated in wild environment and adopted in laboratory. Whereas the2009H1N1and H3N2influenza virus were reconstructed with the bone of A/PR8internal gene in laboratory, thus pre-existing immunity have offered mice excellent protection without significant difference as compared with those vaccinated by NP+M1DNA vaccine.(4) Research about the influence on influenza vaccine vaccination by pre-exposure to influenza. Immune memory elicited by pre-infection of influenza virus, with vaccination of internal gene DNA vaccine, could provide protection against challenge of homotypic and heterotypic influenza virus. Whereas immune gene elicited by pre-infection of influenza virus was reported to produce original antigenic sin, in other words, the existence of immune memory is unfavorable to new vaccine to elicit antibodies, even resulting in antagonism to some extent. To prove the conclusion, in this study, mice were infected by A/PR8influenza virus firstly, and vaccinated by2009H1N1inactivated vaccine,2009H1N1HA DNA and H5N1inactivated vaccine respectively, then challenged with homotypic virus. Antibodies and protective abilities were detected. The results showed that no effect was produced.(5) Research on adjuvant effect of chitosan for inactivated influenza H5N1vaccine. In this study, mice were injected intraperitoneally once or twice with various dosage of inactivated vaccine alone or in combination with chitosan. Antibody titers, residue virus titer in lung, and body weight loss as well as survival rates after challenge were detected. The protective immunity in mice provided by chitosan-adjuvanted inactivated H5N1vaccine was compared with that from a traditional aluminum hydroxide-adjuvanted one. The results showed that the adjuvanted vaccines were more effective than adjuvant-free ones in inducing humoral immune responses, reducing the dosage of antigen, enhancing the abilities against virus infection, reducing residue virus titer in lung and weakening the clinical symptoms of infected mice. Chitosan was comparable to the alum adjuvant in efficacy. These findings indicated that chitosan might be a candidate adjuvant for parenteral administration of inactivated influenza vaccines.