Successful primate immunization with peptides conjugated to purified protein derivative or mycobacterial heat shock proteins in the absence of adjuvants

Abstract

SUMMARYWe have previously shown in mice that antibodies can be induced to synthetic malaria peptides conjugated to myeobacterial antigens, such as purified protein derivative (PPD) or heat shock proteins (hsp), and given in the absence of adjuvants after a previous priming with bacille CalmetteGucrin (BCG), In the present study we investigated this model of itnmunizatJon in the non-human primates, Saimiri sciureus monkeys. Monkeys primed wilh BCG subcutaneously and then imtTiuni,^ed subcutaneously with the Plasmodium falcipaium sporozoitc (NANP)4ii synthetic peptide conjugated to PPD or myeobacterial hsp of 65 or 70 kD, in the absence of adjuvants, produced antipeptide and iinli-sporozoite IgG antibodies. Interestingly, thecarrierejfect ofthc h.sp of 70 kD for the induction of anti-(NANP)4(i antibodies was also observed in the absence ofa previous priming wilh BCG, These data suggest that such a vaccination strategy tnay be applied to humans.

Heat Shock Proteins in Mycobacterium tuberculosis: Involvement in Survival and Virulence of the Pathogen

“…The mycobacterial Hsp65 and Hsp70 acted as carrier molecules in mice previously primed with M. tuberculosis and showed high and long-lasting titers of IgG (Barrios et al, 1992;Perraut et al, 1993). The mycobacterial Hsp65 conjugated to peptides or oligosaccharides in the absence of adjuvants, induced antibodies which cross-reacted well with Hsp homologues from other prokaryotes, but weakly with the human Hsp homologue (Barrios et al, 1994).…”

Vaccination with a potent DNA vaccine targeting B-cell epitopes of hGRP induces prophylactic and therapeutic antitumor activity in vivo

“…In addition, mycobacterial heat shock protein 65 kDa (HSP65) was constructed upstream of GRP6, serving as vector for delivering this B-cell epitopes. 17 Moreover, tandem repeats (1-4) of mycobacterial HSP70 fragment 407-426 18 in linear alignment was inserted into the DNA vaccine downstream of GRP immunogen to analyze whether introduction of this foreign T-helper epitope into DNA vaccine could boost GRP immunogenicity by inducing strong neutralizing auto-Abs against the tumor growth factor sufficiently to be protective in tumor cell challenge.…”

A novel vaccine targeting gastrin-releasing peptide: efficient inhibition of breast cancer growth in vivo

“…But a key problem in developing subunit vaccines is that the immunogenicity of the vaccines is weak. Previous studies have demonstrated that mycobacterial 65 kDa heat shock proteins (HSP65) exhibit strong immunogenicity and contain strong T-cell epitopes presented by major histocompatibility II molecules, and accordingly they have been used as helper T-cell epitopes for delivering B-cell epitopes in vivo (Perraut et al 1993). Thus, HSP65 can be used as suitable and safe carrier molecules for delivering B-cell epitopes to the immune system in vivo in the absence of adjuvants (Barrios et al 1994).…”