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Protection from pathogenic SIVmac challenge following short-term infection with a nef-deficient attenuated virus.

Abstract：

:Infection of rhesus macaques with attenuated SIVmac is, at present, the only strategy which confers significant protection from challenge with wild-type SIVmac grown in monkey PBMC. However, initial results suggest that the protective mechanism does not develop until late after "vaccination" (approx 10 months). As part of a European study using the C8 variant of SIVmac251-32H (containing an in-frame 12-bp deletion in the nef gene), we wished to determine (a) if protection could be achieved against challenge with a "swarm" of SIVmac251-32H produced in monkey cells and (b) if protection could be demonstrated after a short period of infection with the attenuated virus. Eight Indian rhesus macaques were infected with C8 and four were challenged after 10 weeks with 50 MID50 of an uncloned stock of SIVmac251-32H grown in rhesus cells, and the other four were challenged after 20 weeks. Four animals served as naive controls. Three of the four monkeys challenged at 10 weeks and three of those challenged at 20 weeks were protected from productive superinfection. From one monkey in each group it was, however, possible to demonstrate the presence of the wild-type provirus in monkey PBMC by diagnostic PCR and anamnestic immune response. There was no apparent correlation between the levels of binding or neutralizing antibodies on the day of challenge and subsequent protection. Approximately 1 year after infection with the attenuated virus all monkeys were rechallenged with the heterologous SIVsm strain, first with 10-20 MID50 and then with 1000 MID50. Although not all of the SIVsm-inoculated naive controls became productively infected, PCR analysis failed to reveal any evidence for infection of the "immunized" monkeys.

journal_name

Virology

journal_title

Virology

authors

Norley S,Beer B,Binninger-Schinzel D,Cosma C,Kurth R

doi

10.1006/viro.1996.0237

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

195-205

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(96)90237-8

journal_volume

219

pub_type

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