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Title:   Author  item
                                            Baker, Amyitem
                                            MA, WENJUN - IOWA STATE UNIVERSITYitem
                                            Lager, Kellyitem
                                            JANKE, BRUCE - IOWA STATE UNIVERSITYitem
                                            WEBBY, RICHARD - ST JUDE CHILDREN'S RESEARitem
                                            GARCIA-SASTRE, ADOLFO - MOUNT SINAI SCHOOL OF MEDitem
                                            Richt, Juergen
  Submitted to: Vaccine
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 9/6/2007
                                    Publication  Date: 11/1/2007
                                    Citation: Vincent, A.L., Ma, W., Lager, K.M., Janke, B.H., Webby, R.J., Garcia-Sastre, A., Richt, J.A. 2007. Efficacy of intranasal administration of a truncated NS1 modified live influenza virus vaccine in swine. Vaccine. 25:7999-8009.Interpretive Summary: One of the challenges to control and eliminate swine influenza virus (SIV) is that the currently used inactivated influenza virus vaccines do not provide adequate cross-protection against multiple antigenic variants of SIV in the field. In the present study, we first compared intramuscular and intranasal routes of application of a modified live-virus vaccine (MLV) against SIV. We found that the intranasal route was the most effective in inducing immunity in the respiratory tract, the site of infection. Pigs were then vaccinated via the intranasal route and challenged with the wild type parent vaccine strain as well as two different viruses. The intranasally vaccinated pigs were completely protected against challenge with the wild type parent virus. In addition, MLV vaccination provided nearly complete protection against one of the divergent viruses and partial protection from the other divergent influenza virus. These results support the potential for use of MLV against swine influenza virus and suggest the MLV used in these studies may provide broader protection against viruses differing from the vaccine parent strain. These findings will have impact for scientists and potentially swine producers as new and improved vaccination strategies are developed for SIV.
                                Technical Abstract: In the U.S., despite available swine influenza virus (SIV) vaccines, multiple influenza subtypes as well as antigenic and genetic variants within subtypes continue to circulate in the swine population. One of the challenges to control and eliminate SIV is that the currently used inactivated influenza virus vaccines do not provide adequate cross-protection against multiple antigenic variants of SIV in the field.  We previously generated a recombinant H3N2 swine influenza virus (SIV) based on the influenza A/SW/TX/4199-2/98 virus (TX98) containing an NS1 gene expressing a truncated NS1 protein of 126 amino acids, TX98-NS1delta126 virus.  This recombinant strain was demonstrated to be highly attenuated in swine and showed potential for use as a modified live-virus vaccine (MLV) after intratracheal application in pigs. However, this route of inoculation is not practical for vaccination in the field.  In the present study, we first compared intramuscular and intranasal routes of application of the MLV, and found that the intranasal route was superior in priming the local (mucosal) immune response.  Pigs were then vaccinated via the intranasal route and challenged with wild type homologous TX98 H3N2 virus, with a genetic and antigenic variant H3N2 SIV (influenza A/SW/CO/23619/99 virus, CO99) and a heterosubtypic H1N1 SIV (influenza A/SW/IA/00239/2004 virus, IA04).  The intranasally vaccinated pigs were completely protected against homologous challenge. In addition, MLV vaccination provided nearly complete protection against the antigenic H3N2 variant CO99 virus. When challenged with the H1N1 IA04 virus, MLV vaccinated animals displayed reduced fever and virus titers despite minimal reduction in lung lesions. In vaccinated pigs, there was no serologic cross-reactivity by HI assays with the heterologous or heterosubtypic viruses. However, there appeared to be substantial cross-reactivity in antibodies at the mucosal level with the CO99 virus in MLV vaccinated pigs.


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