Strategies to Improve the Effect of Vaccination in the Elderly: the Vaccine Producer's Perspective

SummaryThe weakened immune system of elderly people presents particular challenges in the development of vaccines and vaccination strategies for this population. There are well recognized changes in the function of antigen presenting cells (APCs), T cells and B cells in older people. Several strategies to improve vaccination in the elderly have been explored. The use of adjuvants (e.g. emulsions and Toll-like receptor [TLR] agonists) could trigger more potent activation of APCs. The addition of T helper epitopes to the vaccine antigens could enhance T-cell responses by acting as ‘intrinsic’ adjuvants. The use of interleukin (IL)-7 could improve the expansion of naïve T cells in the elderly, accompanied by a broadened T-cell repertoire. A further means of enhancing antigen presentation and subsequent T-cell activation would be to increase the vaccine dose and/or antigenic content. Vaccination schedules could also be adapted. In particular, vaccination at an earlier age may trigger naïve T cells and subsequent generation of memory cells more efficiently and these cells may be recalled more easily in later life. Vaccination against cytomegalovirus (CMV) early in life has also been proposed to avoid the ‘CMV bias’ of the immune response that is seen in the elderly population. Immunization routes other than by intramuscular or subcutaneous injection may be more efficient, by delivering antigen to sites enriched in APCs such as the epidermis and/or dermis. Finally, the use of polysaccharide–protein conjugates might enhance the level and functionality of antibodies directed against polysaccharides. These different possibilities, alone or in combination, could improve vaccine efficacy in elderly human populations.