Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/30/2009
Publication Date: 12/11/2009
Citation: Kitikoon, P., Vincent, A.L., Janke, B.H., Erickson, B., Strait, E.L., Yu, S., Gramer, M.R., Thacker, E.L. 2009. Swine Influenza Matrix 2 (M2) Protein Contributes to Protection Against Infection with Different H1 Swine Influenza Virus (SIV) Isolates. Vaccine. 28(2):523-531. Interpretive Summary: This study evaluated influenza vaccines in pigs. Vaccines included whole virus inactivated (killed) and a subunit protein vaccine containing the conserved influenza A virus protein matrix 2 (M2). The vaccinated pigs were infected with two different isolates of swine influenza virus (SIV) of the H1 subtype, a match to the whole virus H1N1 vaccine (IA30) and a mismatched H1N2 virus (MN03). The killed vaccine did not protect against live virus challenge with the MN03 SIV isolate. All of the pigs in this group were shown microscopically to have virus levels no different than unvaccinated pigs up to 5 days post infection. In addition, pneumonia caused by the influenza virus was dramatically worse in all of the pigs receiving the mismatched vaccine. The addition of the subunit M2 vaccine at the time of whole virus killed vaccine reduced fever, but not the enhanced pneumonia induced by the vaccine mismatch. The M2 vaccine alone provided partial protection. This study suggests that immunity to influenza virus is complex and there is a risk of enhancing disease when the inactivated vaccine virus is mismatched with the challenge virus, despite the addition of the conserved subunit vaccine.
Technical Abstract: A swine influenza virus (SIV) vaccine-challenge pig model was used to study the potential of the conserved matrix 2 (M2) protein vaccine alone or in combination with an inactivated H1N1 vaccine to protect against H1N1 and H1N2 viruses. The H1N1-vaccine and heterologous H1N2-challenge virus had previously been shown to prolong fever and increase SIV-associated pneumonic lesions. The M2 vaccine in combination with the H1N1 vaccine reduced the H1N2 induced fever but not virus shedding. The M2 vaccine alone reduced respiratory signs and pneumonic lesions to levels similar to the negative control pigs following H1N2 infection. This study found that the M2 protein has potential as a vaccine for SIV-associated disease prevention. However, development of an immune response towards the major envelope HA protein was required to reduce SIV shedding.