IAI Accepts, published online ahead of print on 9 November 2009
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Infect. Immun. doi:10.1128/IAI.00877-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Baculovirus-based nasal drop vaccine confers complete protection against malaria by natural boosting of vaccine-induced antibodies in mice

Shigeto Yoshida*, Hitomi Araki, and Takashi Yokomine

Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi 329-0498, Japan

* To whom correspondence should be addressed. Email: shigeto{at}jichi.ac.jp.


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Abstract

Blood-stage malaria parasites ablate memory B cells generated by vaccination in mice, resulting in diminishing natural boosting of vaccine-induced antibody responses to infection. Here we show the development of a new baculovirus-based Plasmodium yoelii 19-kDa carboxyl terminus of merozoite surface protein 1 (PyMSP119) vaccine capable of circumventing the tactics of parasites in a murine model. The baculovirus-based vaccine displayed PyMSP119 on the surface of the virus envelope in its native three-dimensional structure. Needle-free intranasal immunization of mice with the baculovirus-based vaccine induced strong systemic humoral immune responses with high titers of PyMSP119-specific antibodies. Most importantly, this vaccine conferred complete protection by natural boosting of vaccine-induced PyMSP119-specific antibody responses shortly after challenge. The protective mechanism is a mixed Th1/Th2-type immunity, which is associated with the TLR9-dependent pathway. The present study offers a novel strategy for the development of malaria blood-stage vaccines capable of naturally boosting vaccine-induced antibody responses to infection.