Ej. Verschoor et al., Efforts to broaden HIV-1-specific immunity by boosting with heterologous peptides or envelope protein and the influence of prior exposure to virus, J MED PRIM, 28(4-5), 1999, pp. 224-232
In two previous studies, we have demonstrated the successful protection of
human immunodeficiency virus type 1 (HIV-1)-vaccinated rhesus macaques from
challenge with SHIVSF13 with envelop immunogens derived from the closely r
elated HIV-1(SF2) strain. Here we report on two follow-up studies in which
we aimed to broaden immunity in order to elicit protection from a more dive
rse heterologous challenge with SHIVSF33. In the first study, animals were
boosted once with HIV-1(SF33) V2 and V3 peptides that were cross-linked to
influenza immune-stimulating complexes (ISCOMs). In the second study, monke
ys were boosted twice at 12-week intervals, using a heterologous recombinan
t gp120 derived from HIV-1(SF33) that was either incorporated into ISCOMs o
r mixed with the MF59 adjuvant. In both studies, the animals were challenge
d with 50 monkey infectious doses of SHIVSF33 4 weeks after the final boost
. All controls became readily infected with the heterologous challenge viru
s SHIVSF33. Neither boosting with heterologous SF33 peptides or gp120 affor
ded protection from infection to SF2-vaccinated animals that had previously
resisted SHIVSF13 challenge. These results demonstrate the importance of d
eveloping vaccine strategies that are capable of generating broad immune re
sponses early in the immunization protocol. Furthermore, these findings may
illustrate the potential pitfalls of early antigenic sin.