INDUCTION OF PROTECTIVE POLYCLONAL ANTIBODIES BY IMMUNIZATION WITH A PLASMODIUM-YOELII CIRCUMSPOROZOITE PROTEIN MULTIPLE ANTIGEN PEPTIDE VACCINE

Monoclonal Abs against the repeat region of the circumsporozoite prote in (CSP) completely protect mice against Plasmodium yoelii (Py), but s ynthetic peptide and recombinant protein vaccines designed to produce only Abs to the PyCSP repeat region have never been reported to consis tently provide protection. This lack of protection in the rodent model system has predicted the poor protection achieved in humans after imm unization with synthetic peptide and recombinant protein P. falciparum CSP vaccines and has raised serious questions regarding the capacity for vaccine-induced polyclonal Abs against the CSP to consistently pro tect humans. We now report immunization studies with a multiple Ag pep tide vaccine designed to rely on ''universal'' T epitopes from tetanus toxin to produce T cell help for induction of protective Abs against the repeat region of the PyCSP. When delivered with a nonionic block c o-polymer adjuvant, the vaccine protected 78 to 100% of three inbred s trains of mice, and 100% of outbred mice against P. yoelii sporozoite challenge. Protection was associated with Ab titer, and passive transf er of purified IgG from immune mice protected naive recipients. Simila r protection was achieved when the peptide was encapsulated in liposom es with lipid A and mixed with aluminum hydroxide. By demonstrating fo r the first time solid protection against P. yoelii by polyclonal Abs against the CSP, these data provide the rationale for assessment of a similarly constructed and formulated P. falciparum CSP multiple Ag pep tide vaccine in humans.