Evaluation of the safety and immunogenicity in rhesus monkeys of a recombinant malaria vaccine for Plasmodium vivax with a synthetic toll-like receptor 4 agonist formulated in an emulsion

Joanne M. Lumsden, Sathit Pichyangkul, Utaiwan Srichairatanakul, Kosol Yongvanitchit, Amporn Limsalakpetch, Saule Nurmukhambetova, Jennifer Klein, Sylvie Bertholet, Thomas S. Vedvick, Steven G. Reed, Jetsumon Sattabongkot, Jason W. Bennett, Mark E. Polhemus, Christian F. Ockenhouse, Randall F. Howard, Anjali Yadava*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Plasmodium vivax is the major cause of malaria outside sub-Saharan Africa and inflicts debilitating morbidity and consequent economic impacts in developing countries. In order to produce a P. vivax vaccine for global use, we have previously reported the development of a novel chimeric recombinant protein, VMP001, based on the circumsporozoite protein (CSP) of P. vivax. Very few adjuvant formulations are currently available for human use. Our interest is to evaluate second-generation vaccine formulations to identify novel combinations of adjuvants capable of inducing strong, long-lasting immune responses. In this study rhesus monkeys were immunized intramuscularly three times with VMP001 in combination with a stable emulsion (SE) or a synthetic Toll-like receptor 4 (TLR4) agonist (glucopyranosyl lipid A [GLA]) in SE (GLA-SE). Sera and peripheral blood mononuclear cells (PBMCs) were tested for the presence of antigen-specific humoral and cellular responses, respectively. All groups of monkeys generated high titers of anti-P. vivax IgG antibodies, as detected by enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence assays. In addition, all groups generated a cellular immune response characterized by antigen-specific CD4+ T cells secreting predominantly interleukin-2 (IL-2) and lesser amounts of tumor necrosis factor (TNF). We conclude that the combination of VMP001 and GLA-SE is safe and immunogenic in monkeys and may serve as a potential second-generation vaccine candidate against P. vivax malaria.

Original languageEnglish
Pages (from-to)3492-3500
Number of pages9
JournalInfection and Immunity
Volume79
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

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