Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara

Abstract

Immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. A particular sequence of subunit immunization with pre-erythrocytic antigens of Plasmodium berghei, consisting of single dose priming with plasmid DNA followed by a single boost with a recombinant modified vaccinia virus Ankara (MVA) expressing the same antigen, induced unprecedented complete protection against P. berghei sporozoite challenge in two strains of mice. Protection was associated with very high levels of splenic peptide-specific interferon-gamma-secreting CD8+ T cells and was abrogated when the order of immunization was reversed. DNA priming followed by MVA boosting may provide a general immunization regime for induction of high levels of CD8+ T cells.

Reduced immunogenicity of DNA vaccine plasmids in mixtures

“…Second, recent experiments have shown marked improvements in immunogenicity and efficacy when DNA vaccines are used as part of a heterologous prime-boost vaccination strategy. 19,20,15 It was possible that boosting with recombinant virus would overcome whatever suppressive effect of mixing was observed with DNA vaccines alone. However, in the current experiments, boosting with either of two recombinant vaccinia expressing PfCSP only partially overcame the suppressive effect of mixing on antibody responses to PfCSP (Figure 4a), and had no effect on the suppression of PfCSP-specific IFN-g responses in M9 (Figure 4b).…”

Generation and evaluation of a recombinant modified vaccinia virus Ankara vaccine for rabies

“…Recombinant MVA expressing pre-erythocytic Plasmodium berghei antigens is also envisioned as part of vaccination regime against malaria and is also currently being evaluated in clinical trials [44], [45] and [46]. In addition, recombinant MVA viruses have been shown to be excellent boosters of vaccine induced immunity, particularly when DNA vaccine prime and recombinant MVA boost regimes are employed, but also when attenuated live vaccines are used as primary vaccine [46], [47] and [48].…”

Induction of long‐lasting multi‐specific CD8+ T cells by a four‐component DNA‐MVA/HIVA‐RENTA candidate HIV‐1 vaccine in rhesus macaques

“…Although a great initial insight about vaccine performance and various novel vaccine vector combinations can be obtained in mice [3,4], nonhuman primate (NHP) models were better predictors of the T cell immunogenicity in humans [5][6][7]. A long list of similarities detected between the NHP and human data [6] argues that the NHP model can be used to better inform the clinicians on vaccine potential.…”