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Karen Yam, Angela Brewer, Jyotsana Gupta, Elizabeth Allen, Brian Ward, Long-term immune responses to AS03-adjuvanted, low antigen dose influenza vaccines in BALB/c mice (P4299), The Journal of Immunology, Volume 190, Issue Supplement_1, May 2013, Page 123.13, https://doi.org/10.4049/jimmunol.190.Supp.123.13
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Abstract
During the 2009 pandemic influenza outbreak, a vaccine formulated with the oil-in-water adjuvant AS03 and 25% of the usual antigen dose was selected for administration to Canadians. Since the long-term (LT) immune response to this vaccine remains unclear, our objective is to study AS03-adjuvanted low antigen dose influenza vaccines in mice with a focus on LT immunity. We hypothesize that LT memory following unadjuvanted full-dose vaccine will be superior to adjuvanted low-dose vaccination. Mice received 2 IM injections of influenza A/Uruguay H3N2 split vaccine formulated with 3µg antigen only or low antigen dose with AS03 adjuvant. At 3 weeks post-boost, serum hemagglutination inhibition (HAI) titers were: 276 (3µg unadjuvanted); 1365 (0.03µg+AS03); and 1681 (0.003µg+AS03). Lower antigen doses (0.00003-0.0003µg) with AS03 failed to consistently produce detectable antibodies. LT studies with these same formulations (3µg, 0.03µg+AS03, 0.003µg+AS03) are ongoing for up to 18 weeks post-boost; we are examining spleen and bone marrow cells (eg: ELISpots, cytokine profiles, B cell subsets by flow cytometry). At 1, 3 and 6 weeks post-boost, splenocytes of mice immunized with antigen alone produced higher levels of IL-4 and IL-10 than mice immunized with adjuvanted low-dose vaccines. Conversely, splenocytes from the adjuvanted low-dose groups produced higher levels of IL-2 than those from mice immunized with antigen alone. These differences in LT immunity may affect vaccine efficacy.
