Because of its immunodominancy, and because it is conserved in different geographical isolates of Plasmodium falciparum, the repetitive sequence of the circumsporozoite
protein, (Asn-Ala-
Asn-Pro)n [(NANP)n], has been envisaged for the development of an anti-
falciparum malaria subunit vaccine. However, the murine immune response to (NANP)n
peptides, either carrier-free or coupled to
carrier proteins, was shown to be inducible only by using strong (e.g., Freund's) adjuvants. Furthermore, response to the carrier-free
peptide, administered in adjuvant, is genetically restricted to I-Ab mice. In the present paper, we report that high titers of
antibodies against the NANP repetitive
epitope were obtained in responder C57BL/6 (H-2b) mice when they were primed with live BCG (bacillus Calmette-Guérin Mycobacterium tuberculosis var. bovis) and immunized once with the synthetic
peptide (NANP)40 coupled to
tuberculin purified
protein derivative (
PPD) without the use of any adjuvant. This approach also led to the production of high titers of anti-NANP
antibodies in ASW (H-2s), B10.RIII (H-2r), BALB/c (H-2d), C3H/He (H-2k), and DBA/1 (H-2q) nonresponder mice after two
injections of the conjugate. In both cases, BCG priming was obligatory for the induction of
antibodies reacting with the synthetic
peptide. The levels of anti-NANP
antibodies in nonresponder BALB/c mice were demonstrated to be comparable to the levels induced after PPD-(NANP)40 immunization in Freund's complete or incomplete adjuvant. The
antibodies induced were also capable of recognizing P. falciparum sporozoites in immunofluorescence assays and, furthermore, these
antibodies inhibited the penetration of live sporozoites into human hepatocytes in vitro. This system functioned independently of the subjects' resistance or susceptibility to BCG
infection. Given the widespread natural exposure to mycobacterial
antigens and the extensive use of BCG and
PPD in the human population, this approach might be envisaged for vaccination with
malaria peptides.