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

Infect Immun. 2010 Feb;78(2):595-602. doi: 10.1128/IAI.00877-09. Epub 2009 Nov 9.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Protozoan / blood*
  • Antibodies, Protozoan / immunology
  • Blotting, Western
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique
  • Malaria / prevention & control*
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology*
  • Merozoite Surface Protein 1 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Immunoelectron
  • Plasmodium yoelii / immunology*

Substances

  • Antibodies, Protozoan
  • Malaria Vaccines
  • Merozoite Surface Protein 1