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.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01AT002952-01A2
Application #
7219148
Study Section
Special Emphasis Panel (ZAT1-JH (16))
Program Officer
Duffy, Linda C
Project Start
2010-09-30
Project End
2012-08-31
Budget Start
2010-09-30
Budget End
2011-08-31
Support Year
1
Fiscal Year
2010
Total Cost
$1,310,980
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Solano-Aguilar, Gloria; Molokin, Aleksey; Botelho, Christine et al. (2016) Transcriptomic Profile of Whole Blood Cells from Elderly Subjects Fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG) in a Phase I Open Label Study. PLoS One 11:e0147426
Doron, Shira; Hibberd, Patricia L; Goldin, Barry et al. (2015) Effect of Lactobacillus rhamnosus GG Administration on Vancomycin-Resistant Enterococcus Colonization in Adults with Comorbidities. Antimicrob Agents Chemother 59:4593-9
Eloe-Fadrosh, Emiley A; Brady, Arthur; Crabtree, Jonathan et al. (2015) Functional dynamics of the gut microbiome in elderly people during probiotic consumption. MBio 6:
Hibberd, Patricia L; Kleimola, Lauren; Fiorino, Anne-Maria et al. (2014) No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a phase I open label study to assess safety, tolerability and cytokine responses. PLoS One 9:e113456
Eloe-Fadrosh, Emiley A; Rasko, David A (2013) The human microbiome: from symbiosis to pathogenesis. Annu Rev Med 64:145-63
Petschow, Bryon; Doré, Joël; Hibberd, Patricia et al. (2013) Probiotics, prebiotics, and the host microbiome: the science of translation. Ann N Y Acad Sci 1306:1-17