Influenza Vaccination in the Elderly: Seeking New Correlates of Protection and Improved Vaccines

Abstract

Influenza is foremost among all infectious diseases for an age-related increase in risk for serious complications and death. Determining the benefit of current influenza vaccines is largely limited to epidemiologic studies, since placebo-controlled trials of influenza vaccines are no longer considered ethical in the older adult population. Vaccine effectiveness is calculated from the relative reduction in influenza outcomes in individuals who elect to be vaccinated compared with those who do not, the assumptions for which are diverse and have led to considerable controversy as to the exact benefit of influenza vaccination in older adults. In spite of this controversy, there is no doubt that new influenza vaccine technologies are needed to improve protection and reverse the trend of rising hospitalization and death rates related to influenza in older adults despite widespread influenza vaccination programs. This article will review the challenges to new vaccine development, explore the potential correlates of protection against influenza, and describe how new vaccine technologies may improve protection against complicated influenza illness in the older adult population.

Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans

“…The HI response has previously been shown to decrease with age in both mice and humans [9, 15, 17]. We analyzed the HI response in the subjects in this study in order to test whether the in vivo response to the influenza vaccination (HI) was consistent with a decreased functional response in intrinsic B cells (AID).…”

Age effects on B cells and humoral immunity in humans

“…Approximately 40,000 deaths are attributed to influenza, with most of the affected being the elderly and those patients with compromised immune systems. The serologic response to influenza virus vaccine varies with age (de Bruijn et al, 1999; Goodwin et al, 2006; McElhaney, 2008; McMurry et al, 2008). Successive annual vaccinations increase protection against influenza (Ahmed et al, 1995; Keitel et al, 1988; Thompson et al, 2004), suggesting that cellular and humoral immune mechanisms are important for protection in elderly individuals.…”

Vaccinomics and a New Paradigm for the Development of Preventive Vaccines Against Viral Infections

“…Further investigation led to a greater understanding of the role of antibodies in neutralization, opsonization, hemagglutination, and complement fixation. For many pathogens these functional activities are now thought to better correlate with disease protection (Amanna et al, 2008;Feng et al, 2009;Mascola and Montefiori, 2010;McElhaney, 2008).…”