Older adults aged 65 and over account for approximately 90% of deaths associated with influenza and pneumonia. Deaths due to influenza have increased substantially over the last 20 years due to the aging of the population in the United States. The influenza vaccine is the first line of defense against influenza. The parenterally administered inactivated influenza vaccine (IIV) is recommended for all adults aged 65 and over, but the mucosally administered live attenuated influenza vaccine (LAIV) has not been shown to be efficious in the prevention of influenza in individuals aged 50 and older. Even in studies where both IIV and LAIV have been co-administered to the elderly population, there is room for improvement in the immune response to both vaccines. In vitro studies and animal data show that probiotics, particularly Lactobacillus GG (LGG), have immunomodulatory properties. Preliminary data from several studies of healthy volunteers suggest that LGG boosts the immune response to mucosally administered vaccines such as oral Salmonella typhi, rotavirus and polio virus. We propose to conduct a double-blind randomized placebo controlled Phase l/ll clinical trial in adults aged 65 and older to evaluate whether orally administered LGG is effective in enhancing the immunogenicity of either IIV alone or the combination of IIV and LAIV. One hundred and four subjects will be recruited into the study, 26 will receive IIV+LAIV + oral LGG, 26 will receive IIV+LAIV and oral placebo, 26 will receive IIV + oral LGG and 26 will receive IIV and oral placebo. The latter two groups will also receive a nasally administered placebo to match LAIV administration. Blood and nasal specimens will be collected weekly for four weeks to evaluate the initial mucosal and systemic immune response to the immunization. Additional blood and nasal specimens will be collected at the end of the influenza season. Subjects will be followed every two weeks following immunization throughout the influenza season to assess symptoms and have specimens obtained for viral culture if they develop influenza like illnesses. This study has the potential to provide insight into a novel alternative approach to improve the immune response of the influenza vaccines in the elderly.
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