Baculovirus-based nasal drop vaccine confers complete protection against malaria by natural boosting of vaccine-induced antibodies in mice.
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 vaccine comprising a baculovirus-based Plasmodium yoelii 19-kDa carboxyl terminus of merozoite surface protein 1 (PyMSP1(19)) capable of circumventing the tactics of parasites in a murine model. The baculovirus-based vaccine displayed PyMSP1(19) 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 PyMSP1(19)-specific antibodies. Most importantly, this vaccine conferred complete protection by natural boosting of vaccine-induced PyMSP1(19)-specific antibody responses shortly after challenge. The protective mechanism is a mixed Th1/Th2-type immunity, which is associated with the Toll-like receptor 9 (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.
Yoshida
Shigeto
S
Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. shigeto@jichi.ac.jp
Araki
Hitomi
H
Yokomine
Takashi
T
D000281:Administration, Intranasal; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016253:Microscopy, Immunoelectron; D010967:Plasmodium yoelii / Q000276:immunology*
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1