Lambert, Nathaniel

Abstract Pre and post-licensure studies have supported the safety of the intranasally administered live, attenuated influenza vaccine (LAIV). The objective of this study was to measure changes to the nasal microbiome in subjects who received LAIV. We hypothesized that administration would result in only a transient alteration of the nasal microbiome. To test this hypothesis, we swabbed the anterior nares just before vaccination (Day 0), and on Day 7 and Day 28. We performed next-generation sequencing on amplified 16s rRNA genes. There was a significant increase in alpha diversity (Observed, CHAO, and ACE) from Days 0 to 7 (p = 0.02, 0.00, 0.01; respectively) and Days 0 to 28 (p = 0.05, 0.03, 0.05; respectively). When measuring differences in specific observed taxanomic units (OTUs), we identified a significant increase in Flavobacteriaceae and Enterobacteriaceae after vaccination. These data suggest that LAIV may increase the ability of these less abundant OTUs to establish a community niche and, therefore, could be clinically relevant. We have begun to investigate the second objective of this study, which is to correlate microbiome composition with mucosal immunity to influenza virus. To our knowledge, this is the first study to investigate LAIV-induced alterations to the human microbiome. These data may lead to a better understanding of the influences of the host microbiome on the response to vaccine, and perhaps infection.

Abstract We have previously demonstrated that inbred B10.T(6R) mice are resistant to Yesinia pestis (KIM5 strain) and resistance decreases with age. It has been shown that Y. pestis is cleared by neutrophil engulfment. We evaluate here the potential contribution of IL-1β, a proinflammatory cytokine important for neutrophil recruitment and activation. IL-1β levels were measured from spleens and sera collected 60 and 72 hour post infection from young (resistant) and middle-aged (susceptible) B10.T(6R) mice and control (susceptible) C57BL/6. Splenic IL-1β production was statistically higher in young B10.T(6R), compared with both middle-aged B10.T(6R) and C57BL/6 mice. Serum IL-1β levels were also moderately higher in young B10.T(6R) mice when compared to middle aged B10.T(6R) and C57BL/6 mice. IL-1β produced by Y. pestis-infected peritoneal-derived macrophages taken from uninfected young and middle-aged B10.T(6R) mice and C57BL/6 mice was measured at 2,4,8 and 24 hour. IL-1β levels were significantly elevated in peritoneal macrophages infected in vitro from young B10.T(6R) mice compared to decreased levels in both middle-aged B10.T(6R) and C57BL/6 derived peritoneal macrophages. These studies suggest a direct correlation between elevated IL-1β levels and resistance to Y. pestis infection observed in young B10.T(6R) mice.