Viral vector vaccines make memory T cells against malaria

Abstract

Vaccines that comprise attenuated viral vectors encoding antigens from target pathogens generate potent T-cell responses. One such pathogen is malaria, and in particular the liver stage of its life cycle. Immunogenicity and efficacy studies in animals and humans have revealed the generation of memory T cells of both the central and effector phenotypes, depending on the viral vectors used in the malaria vaccination regime (viral species and serotype, combination and sequence for prime-boost) and suggest a divergence in their protective role. Being able to influence the memory T-cell make-up in a rational manner may allow us to develop more efficacious vaccines.

Figure 1

T-cell priming associated with viral vector immunization. Potential pathways leading to T-cell responses [effector-memory T cells (T_EM) and central-memory T cells (T_CM)] are generated by viral vector vaccines. Viruses may infect dendritic cells (DCs) for direct priming of T cells, or infected DCs may die and provide antigens and activation signals for cross-priming via other DCs. DCs migrate to local lymph nodes (LNs) and can prime T_EM and T_CM cells simultaneously in the parallel pathway, or can prime T_EM cells, which differentiate into T_CM cells in the linear pathway. T_EM rapidly produce effector molecules. T_CM possess receptors for homeostatic proliferation. Ag, antigen; IFN-γ, interferon-γ; IL, interleukin; TNF-α, tumour necrosis factor-α.

Figure 2

Possible kinetics of vaccine regimen-induced immune response in humans. Two prime immunizations with vaccines such as recombinant DNA or FP9 allow the generation of sufficient T cells to then be boosted significantly by modified vaccinia Ankara (MVA), such that effector T-cell responses are easily detected and are potentially protective from infectious challenge.