Improving the immunogenicity and protective efficacy of a whole-killed malaria blood-stage vaccine by chloroquine.

A whole-killed malaria blood-stage vaccine (WKV) is promising in reducing the morbidity and mortality of malaria patients, but its efficacy needs to be improved. We found that the antimalarial drug chloroquine could augment the protective efficacy of the WKV of Plasmodium yoelii. The direct antimalarial effect of chloroquine on parasites during immunization could be excluded, as the administration of chloroquine or chloroquine plus alum every two weeks had a slight effect on parasitemia, and an immunization with NP-KLH (4-hydroxy-3-nitrophenylacetyl Keyhole Limpet Hemocyanin) plus chloroquine could significantly promote the generation of NP-specific antibodies. Additionally, alum was required for chloroquine to augment the immunogenicity of the pRBC lysate. Chloroquine did not promote the parasite-specific CD4+ T-cell responses, but significantly enhanced the WKV-induced germinal centre B cell reactions, class-switch recombination and secretion of functionally protective antibodies to plasmodium. The elevated parasite-specific antibodies were demonstrated to largely contribute to the chloroquine-enhanced protective immunity. Thus, we report that chloroquine could be used as an adjuvant to enhance the protective immunity of WKVs through promoting humoral responses.

Whole-Killed Blood-Stage Vaccine: Is It Worthwhile to Further Develop It to Control Malaria?

Major challenges have been encountered regarding the development of highly efficient subunit malaria vaccines, and so whole-parasite vaccines have regained attention in recent years. The whole-killed blood-stage vaccine (WKV) is advantageous as it can be easily manufactured and efficiently induced protective immunity against a blood-stage challenge, as well as inducing cross-stage protection against both the liver and sexual-stages. However, it necessitates a high dose of parasitized red blood cell (pRBC) lysate for immunization, and this raises concerns regarding its safety and low immunogenicity. Knowledge of the major components of WKV that can induce or evade the host immune response, and the development of appropriate human-compatible adjuvants will greatly help to optimize the WKV. Therefore, we argue that the further development of the WKV is worthwhile to control and potentially eradicate malaria worldwide.