A recombinant prime, peptide boost vaccination strategy can focus the immune response on to more than one epitope even though these may not be immunodominant in the complex immunogen

Rhesus monkeys were successfully vaccinated using a strategy of priming with a candidate envelope subunit vaccine and boosting with synthetic peptides. Priming was carried out with recombinant HIV-1 SF2 envelope glycoprotein incorporated into ISCOMs, following the attachment of a lipid tail. Peptide...

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Bibliographic Details
Published in:Vaccine 1997-10, Vol.15 (15), p.1661-1669
Main Authors: Davis, David, Morein, Bror, Åkerblom, Lennart, Lövgren-Bengtsson, Karin, van Gils, Mariëlle E., Bogers, Willy M.J.M., Teeuwsen, Vera J.P., Heeney, Jonathan L.
Format: Article
Language:English
Subjects:
AIDS Vaccines - immunology
AIDS/HIV
Amino Acid Sequence
Animals
avoiding enhancement
Biological and medical sciences
candidate vaccine
Epitopes
Fundamental and applied biological sciences. Psychology
HIV Antibodies - blood
HIV Envelope Protein gp120 - immunology
HIV-1 envelope glycoprotein
Humans
Immunization, Secondary
Macaca mulatta
Microbiology
Molecular Sequence Data
neutralization escape
peptide boosting
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Vaccines, Synthetic - immunology
Virology
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Summary:Rhesus monkeys were successfully vaccinated using a strategy of priming with a candidate envelope subunit vaccine and boosting with synthetic peptides. Priming was carried out with recombinant HIV-1 SF2 envelope glycoprotein incorporated into ISCOMs, following the attachment of a lipid tail. Peptides, covalently linked to ISCOMs, representing linear sequences within the V2 and V3 regions, were used to boost functional antibodies to neutralizing epitopes in both of these regions. Injections with these peptide formulations substantially increased the titre of serum neutralizing antibodies from low or undetectable levels. In addition to completely neutralizing the homologous HIV-1 SF2 strain, these sera also neutralized the escape variant, HIV-1 SF13. However, no antibodies were boosted which could compete with human, neutralizing monoclonal antibodies recognising conformational epitopes. The peptides also boosted antibodies to a peptide whose sequence lies close to the V2 region neutralizing epitope but does not overlap with it. Importantly, the level of antibodies to an unrelated epitope associated with enhancement of HIV-1 SF13 continued to fall after the peptide boost. Successful protection against challenge with chimeric simian immunodeficiency virus expressing HIV-1 SF13 envelope glycoproteins (SHIV SF13) may be due to an increase in the ratio of neutralizing to enhancing antibodies by selectively boosting with peptides to critical neutralizing epitopes.
ISSN:0264-410X
1873-2518
DOI:10.1016/S0264-410X(97)00084-4