Relevance of long-lived CD8(+) T effector memory cells for protective immunity elicited by heterologous prime-boost vaccination

Abstract

Owing to the importance of major histocompatibility complex class Ia-restricted CD8(+) T cells for host survival following viral, bacterial, fungal, or parasitic infection, it has become largely accepted that these cells should be considered in the design of a new generation of vaccines. For the past 20 years, solid evidence has been provided that the heterologous prime-boost regimen achieves the best results in terms of induction of long-lived protective CD8(+) T cells against a variety of experimental infections. Although this regimen has often been used experimentally, as is the case for many vaccines, the mechanism behind the efficacy of this vaccination regimen is still largely unknown. The main purpose of this review is to examine the characteristics of the protective CD8(+) T cells generated by this vaccination regimen. Part of its efficacy certainly relies on the generation and maintenance of large numbers of specific lymphocytes. Other specific characteristics may also be important, and studies on this direction have only recently been initiated. So far, the characterization of these protective, long-lived T cell populations suggests that there is a high frequency of polyfunctional T cells; these cells cover a large breadth and display a T effector memory (TEM) phenotype. These TEM cells are capable of proliferating after an infectious challenge and are highly refractory to apoptosis due to a control of the expression of pro-apoptotic receptors such as CD95. Also, they do not undergo significant long-term immunological erosion. Understanding the mechanisms that control the generation and maintenance of the protective activity of these long-lived TEM cells will certainly provide important insights into the physiology of CD8(+) T cells and pave the way for the design of new or improved vaccines.

Keywords: CD8; adenovirus; memory; vaccines.

FIGURE 1

Phenotype of specific CD8⁺ T cells elicited by heterologous prime-boost vaccination using recombinant plasmid DNA and AdHu5. Prime-boost regimen was performed as detailed described by Rigato et al. (2011). Mice were primed i.m. with plasmid DNA (100 µg) and boosted 21 days later with AdHu5 (2 × 10⁸) both expressing the gene encoding the amastigote surface protein-2 of T. cruzi. Expression of distinct adhesion/activation receptors on the surface of splenic CD8⁺ specific T cells is shown at day 14 or day 98 after the boost immunization.

FIGURE 2

Expression of distinct adhesion/activation receptors on the surface of specific CD8⁺ T cells elicited by either T. cruzi infection or recombinant AdHu5 immunization (Vasconcelos et al., 2012). Mice were infected s.c. with T. cruzi (150 blood stream trypomastigotes) or immunized i.m. with AdHu5 (2 × 10⁸ pfu) expressing the gene encoding the amastigote surface protein-2 of T. cruzi 19 days earlier.

FIGURE 3

The proposed pathway of activation of specific CD8⁺ T cells following prime-boost vaccination and infection (based on Vasconcelos et al., 2012). Prime-boost regimen was performed as detailed described by Rigato et al. (2011). Mice were primed i.m. with plasmid DNA (100 µg) and boosted 21 days later with AdHu5 (2 × 10⁸) both expressing the gene encoding the amastigote surface protein-2 of T. cruzi. Mice were infected s.c. with T. cruzi (150 blood stream trypomastigotes).