The appearance of escape variants in vivo does not account for the failureof recombinant envelope vaccines to protect against simian immunodeficiency virus
N. Almond et al., The appearance of escape variants in vivo does not account for the failureof recombinant envelope vaccines to protect against simian immunodeficiency virus, J GEN VIROL, 80, 1999, pp. 2375-2382
The presence or evolution of immune escape variants has been proposed to ac
count for the failure of recombinant envelope vaccines to protect macaques
against challenge with simian immunodeficiency virus (SIVmac), To address t
his issue, two groups of three cynomolgus macaques were immunized with reco
mbinant SIV Env vaccines using two different vaccine schedules. One group o
f macaques received four injections of recombinant SIV gp120 in SAF-1 conta
ining threonyl muramyl dipeptide as adjuvant, A second group were primed tw
ice with recombinant vaccinia virus expressing SIV gp160 and then boosted t
wice with recombinant SIV gp120. Both vaccine schedules elicited neutralizi
ng antibodies to Env, However, on the day of challenge, titres of anti-Env
antibodies measured by ELISA were higher in macaques primed with recombinan
t vaccinia virus. Following intravenous challenge with 10 monkey infectious
doses of the SIVmac J5M challenge stock, five of the six immunized macaque
s and all four naive controls became infected. The virus burdens in PBMC of
macaques that were primed with recombinant vaccinia virus were lower than
those of naive controls, as determined by virus titration and quantitative
DNA PCR, Sequence analysis was performed on SIV env amplified from the bloo
d of immunized and naive infected macaques, No variation of SIV env sequenc
e was observed, even in macaques with a reduced virus load, suggesting that
the appearance of immune escape variants does not account for the incomple
te protection observed. In addition, this study indicates that the measurem
ent of serum neutralizing antibodies may not provide a useful correlate for
protection elicited by recombinant envelope vaccines.