The Plasmodium falciparum (P. falciparum) circumsporozoite (CS) protein (CSP) is a major vaccine target for preventing malaria infection. Thus, developing strong and durable antibody and T cell responses against CSP with novel immunogens and potent adjuvants may improve upon the success of current approaches. Here we compared four distinct full-length P. falciparum CS proteins expressed in Escherichia coli (E.coli) or yeast (Pichia pastoris) for their ability to induce immunity and protection in mice when administered with poly-ICLC as an adjuvant. CS proteins expressed in E.coli induced high titer antibody responses against the NANP repeat region and potent CSP-specific CD4+ T cell responses. Moreover, E.coli ... More
The Plasmodium falciparum (P. falciparum) circumsporozoite (CS) protein (CSP) is a major vaccine target for preventing malaria infection. Thus, developing strong and durable antibody and T cell responses against CSP with novel immunogens and potent adjuvants may improve upon the success of current approaches. Here we compared four distinct full-length P. falciparum CS proteins expressed in Escherichia coli (E.coli) or yeast (Pichia pastoris) for their ability to induce immunity and protection in mice when administered with poly-ICLC as an adjuvant. CS proteins expressed in E.coli induced high titer antibody responses against the NANP repeat region and potent CSP-specific CD4+ T cell responses. Moreover, E.coli derived CS proteins in combination with poly-ICLC induced potent multi-functional (IL-2+/TNFα+/IFN-γ+) CD4+ effector T-cell responses in blood, spleen and particularly in the liver. Using transgenic Plasmodium berghei expressing the repeat region of P. falciparum CSP (Pb-CS(Pf)) we showed that there was a 1-4 log decrease in malaria ribosomal RNA in the liver following a high dose challenge and ∼ 50% sterilizing protection with a low dose challenge compared to the controls. Protection was directly correlated with high-level antibody titers but not CD4+ T cell responses. Finally, protective immunity was also induced using GLA/SE as adjuvant, which also correlated with high antibody titers yet significantly less potent CD4+ T cell immunity than poly-ICLC. Overall, these data suggest that full-length CS proteins and poly-ICLC or GLA/SE offer a simple vaccine formulation to be used alone or in combination with other vaccines for preventing malaria infection.
