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Vaccines for Improved Cellular Immunity to Influenza

G. Pawelec,J. Mcelhaney

Published 2018 in EBioMedicine

ABSTRACT

Influenza disease remains a major global public health problem, especially for the elderly, despite intensive efforts to develop more effective vaccines. The seasonal vaccines currently in use suffer from many disadvantages, particularly their poor capacity to elicit cellular immunity and the strain specificity of the antibody response. The selection of target strains is based on prediction of dominant emerging strains in the upcoming season, which may not be altogether accurate. Many efforts in the search for a “universal” influenza vaccine have been directed towards eliciting antibodies binding to the stem region of the viral hemagglutinin conserved between strains, rather than the highly variable globular head domain (Ekiert and Wilson, 2012). However, there is a great deal of evidence suggesting that optimal protection against clinical disease correlates more closely with the ability of the vaccine to stimulate T cell responses than with the antibody titers that are routinely assessed as a surrogate for vaccine efficacy (McElhaney et al., 2006). Indeed, this is underlined by findings from epidemiological studies showing that the presence of pre-challenge T cells responsive to influenza A nucleoprotein (NP) correlatedwith some protection against infection, even in the absence of antibodies (Hayward et al., 2015). An ideal vaccine would therefore be an “off-the-shelf” product capable of eliciting long-lasting protective T-cell and B cell-mediated immunity independent of the particular viral strains in circulation at any one time, and which is equally effective in at-risk populations, such as the elderly or diabetics (Remschmidt et al., 2015). The EBioMedicine paper by Coughlan et al. (2018–in this issue) describes significant steps taken in this direction in a phase I clinical trial of vaccines designed to boost such T cell responses in both younger and older adults. Testing new vaccines in the elderly is extremely important because older people commonly respond poorly to current vaccines, most likely primarily due to deficits in antigen presentation by dendritic cells and T cell responses rather than any intrinsic inability of their B cells to produce antibodies (van Duin et al., 2007). Building on long-standing earlier investigations (Lillie et al., 2012), Coughlan et al. (2018–in this issue) determined the safety of heterologous vaccinationwith the samematrix protein-1 (M1) and NPmoieties delivered by two different viral vectors in younger and older people. Vaccine safety was assessed and stimulation of T cell

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