Synthetic Vaccines against Friend Murine Leukaemia Virus-induced Erythroleukaemia: in vivo and in vitro Studies with Synthetic Oligopeptides and Sequence-specific Antisera
Abstract:SUMMARYBiological activities of antisera against synthetic oligopeptides were examined. The peptide antisera were directed against amino acids 6 to 12 (pepl), 124 to 131 (pep2), 256 to 262 (pep3), 283 to 290 (pep4) and 434 to 441 (pep5) of the viral envelope glycoprotein (gp70). Peptide-specific antisera did not neutralize viral infectivity. However, antibodies to pep4 and pep5, which bound to the hydrophobic part of gp70, mediated the complement-dependent lysis of Friend murine leukaemia virus (FLV)-infected … Show more
“…Previously protective immunity against FV has been induced in mice using killed virions (43), purifi ed envelope protein (44,45), or envelope peptides (46). Furthermore, this system might have particular relevance to the human immunodeficiency virus (HIV) infection because both HIV and FV are capable of induction of profound immunosuppression during the course of infection.…”
Section: Induction Of Protective Immunity To Fvmentioning
“…Previously protective immunity against FV has been induced in mice using killed virions (43), purifi ed envelope protein (44,45), or envelope peptides (46). Furthermore, this system might have particular relevance to the human immunodeficiency virus (HIV) infection because both HIV and FV are capable of induction of profound immunosuppression during the course of infection.…”
Section: Induction Of Protective Immunity To Fvmentioning
“…for FMDV (Bittle et al, 1982;Dimarchi et al, 1986) and HBV (Itoh et al, 1986;Thornton et al, 1987). For other viruses, like murine hepatitis virus (Talbot et al, 1988), Friend murine leukaemia virus (Bayer & Hunsmann, 1987), influenza virus (MUller et al, 1982) and herpes simplex virus (Eisenberg et al, 1985;Weijer et al, 1988), the neutralizing and protective properties of antipeptide antibodies have been weak or absent. Furthermore, a problem in the development of peptide vaccines is that for many viral diseases it is not possible to measure protection, owing to the lack of a suitable animal model.…”
Semliki Forest virus (SFV) infection of mice was used as a model to study the applicability of synthetic peptides containing only linear epitopes as viral vaccines. The identification of linear epitopes with vaccine potential on the E2 membrane protein of SFV was based on the binding of SFV-specific antibodies to a set of overlapping synthetic hexapeptides (Pepscan) representing the whole E2 amino acid sequence. The 14 available E2-specific monoclonal antibodies which were protective in vivo proved to be unsuitable for the identification of linear epitopes because they recognized only conformational epitopes, as indicated by their lack of reactivity with unfolded, reduced E2 protein on immunoblots. Three epitopes were detected with polyclonal anti-SFV serum at amino acid positions 135 to 141,177 to 185 and 240 to 246 of the E2 protein. Synthetic peptides containing these epitopes were coupled to a carrier protein and tested as a vaccine. Mice immunized with the peptide containing amino acids 240 to 255 of protein E2 were protected against a challenge with virulent SFV but protection of mice immunized with the peptides containing amino acids 126 to 141 or 178 to 186 was only marginally better than that of controls. The prechallenge sera of most peptide-immunized mice reacted with SFVinfected cells but none of these sera neutralized the virus in vitro. However, protection of mice correlated well with SFV-specific antibody titre, suggesting antibody-mediated protection.
“…Synthetic peptides corresponding to potential antigenic sites may be useful tools for the immunological characterization of gp85. In addition, peptides mimicking epitopes of defined antigenicity are candidate antigens for incorporation into a synthetic vaccine, as shown earlier using Friend murine leukaemia virus (Bayer & Hunsmann, 1987). Such a subunit vaccine preparation has a distinct advantage, as the region of pl5E that suppresses the immune response (Snyderman & Cianciolo, 1984) and antigenic sites inducing enhancing antibodies can be excluded.…”
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