1160. H1N1 Cross Reactive Adaptive immune Induced by Seasonal Intranasal Live-Attenuated Influenza Vaccine
Session: Poster Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011
Room: Poster Hall B1
Background: 

Re-assortment of influenza viruses renders the antibody responses directed at hemagglutinin largely ineffective. Generating cross protective responses has been a goal of influenza vaccine design. Studies suggest that the use of a live, mucosally-administered vaccine may result in superior induction of cellular immunity leading to cross reactivity, however, the presence of blocking antibodies at the mucosa may decrease the ability of live virus to generate a cellular immune response. We sought to determine the cross reactive responses induced by live attenuated influenza vaccine in a vaccine naive population.

Methods: 

The research was approved by local ethics boards.   Sixty HIV seronegative women from a cohort in Nairobi, Kenya were enrolled. Blood and mucosal samples were obtained prior to vaccine administration and after 1,7, 30 days and 4-6 month after enrolment.  Plasma levels of cytokines were determined using 19 cytokine bead array. PBMC’s were stimulated ex-vivo with Influenza A/H1N1Brisbane, the H1N1 strain included in the seasonal vaccine formulation as well as with pandemic A/H1N1.  Cellular responses were analyzed using  flow cytometry including markers of cell lineage and immune activation and cytokines using intracellular staining. Proliferation and NK function were also assessed using two separate flow cytometry panels. Levels of cytokines in the culture supernatant following stimulation were measured using 19 cytokine bead array.

Results: 

No significant increases in immune activation, cytokine production and proliferation by CD4 and CD8 T lymphocytes were seen following vaccination. Increase in stimulated cytokine levels- IL-6, MIP-1α and IP-10 were observed following immunization. High pre-existing anti vaccine (Bris-92% had high titres) and pandemic (California- 44.1%) H1N1 IgG titres were seen, with no further increase following LIV administration.

Conclusion: 

The modest ability of a LIV to induce cellular responses against vaccine and non-vaccine strains may be the results of high level of pre-existing mucsosal and systemic humoral responses, decreasing antigen availability and prohibiting the generation of robust cross-reactive influenza responses. Further analysis of the mucosal responses is warranted.


Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

Yoav Keynan, MD, Internal Medicine and Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada; Community health Sciences, University of Manitoba, Winnipeg, MB, Canada, Adrienne FA Meyers, PhD, Medical Microbiology, Public Health Agency, Canada; University of Manitoba; University of Nairobi, Winnipeg, MB, Canada, Makubo Kimani, MD, University of Nairobi, Nairobi, Kenya, Joshua Kimani, MD, Medical Microbiology, University of Nairobi, Nairobi, Kenya, Francis A Plummer, MD, Medical Micorbiology, Public Health Agency of Canada, University of Manitoba, Winnipeg, MB, Canada, T. Blake Ball, PhD, Medical Microbiology, Immunology, Public Health Agency of Canada, Winnipeg, MB, Canada and Keith R. Fowke, PhD, Medical Microbiology and Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada

Disclosures:

Y. Keynan, None

A. F. Meyers, None

M. Kimani, None

J. Kimani, None

F. A. Plummer, None

T. B. Ball, None

K. R. Fowke, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.