GILES BM, Bissel SJ, Craigo JK, Dealmeida DR, et a. Elicitation of anti-1918 influenza immunity early in life prevents morbidity and lower lung infection by 2009 pandemic H1N1 influenza in aged mice. J Virol. 2011
The "Spanish" influenza pandemic of 1918 was responsible for 40 to 50 million deaths and is antigenically similar to the swine lineage 2009 pandemic influenza virus. Emergence of the 2009 pandemic from swine into humans has raised the possibility that low-levels of cross protective immunity to past shared epitopes could confer protection. In this study, influenza virus-like particles (VLP) were engineered to express the HA and NA genes from the 1918 influenza virus to evaluate the duration of cross-protection to the H1N1 pandemic strain by vaccinating young mice (8-12 weeks) and then allowing the animals to age to 20 months. This immunity was long-lasting with homologous receptor blocking antibodies detected throughout the lifespan of vaccinated mice. Furthermore, the 1918 VLP fully protected aged mice from 2009 pandemic H1N1 virus challenge 16 months after vaccination. Histopathological assessment showed that aged vaccinated mice had significant protection from alveolar infection, but less protection of the bronchial tissue than adult vaccinated mice. Additionally, passive transfer of immune serum from aged vaccinated mice resulted in protection from death, but not morbidity. This is the first report describing the lifelong duration of cross-reactive immune responses elicited by a 1918 VLP vaccine in a murine model. Importantly, these life-long immune responses did not result in decreased total viral replication, but did prevent infection of the lower respiratory tract. These findings show that immunity acquired early in life can restrict the anatomical location of influenza viral replication, rather than preventing infection, in the aged.
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