Content area
Full Text
Background
The elderly population has the highest risk of morbidity and mortality from influenza infection, and is the population least likely to respond to inactivated influenza vaccine [1,2] . In generating protective immunity, antigens introduced through vaccination activate innate immune pathways that trigger adaptive responses leading to the production of humoral immunity [3] . Identifying early innate immune markers that are associated with humoral immune response to influenza vaccine may help distinguish between those who are likely to generate protective immunity shortly after vaccination from those who are not. This is of particular importance in older individuals whose immune systems are less capable of responding to vaccines and infections. This immunosenescence, or age-related decline in immune function, has a significant impact on health and longevity in older individuals. In the long term, early biomarkers may also inform development of novel influenza vaccines to generate protective immunity more reliably in the elderly.
The hemagglutination inhibition assay (HAI) has been used as the correlate of protection for influenza vaccine response since the latter half of the 20th century [1,4] . Studies in healthy adults and children have found that an HAI titer of 1:40 corresponds with a 50% reduction in influenza infection and is considered the benchmark for seroprotection; a four-fold rise in HAI titer has been conventionally used to indicate immunologic response to vaccination (i.e., seroconversion) [1,4-7] . At this time, influenza vaccines must demonstrate adequate HAI response for licensure by the Food and Drug Administration (FDA); however, HAI alone is insufficient to characterize humoral response to influenza vaccination, especially in older adults [6-8] . Newer assays such as viral neutralization antibody (VNA) and influenza B cell ELISPOT offer complementary assessment of protective antibody responses through analysis of inactivation of influenza infectivity, and influenza-specific IgG secreting B cells, respectively [7,9,10] . Further validation is needed to evaluate the use of these assays as correlates of protective immunity from influenza vaccination with regard to vaccine efficacy and licensure.
In this study, we describe a cohort of older adults who received 2010-2011 inactivated influenza vaccine and present the results of statistical modeling to identify early innate immune markers that are associated with humoral immune responses to influenza A/California/2009 (H1N1), as measured through HAI, microneutralization, and B cell ELISPOT.