학술논문
Immunization with single-cycle SIV significantly reduces viral loads after an intravenous challenge with [SIV.sub.mac]239
Document Type
Report
Author
Source
PLoS Pathogens. January 2009, Vol. 5 Issue 1
Subject
Language
English
ISSN
1553-7366
Abstract
Introduction The search for a safe and effective AIDS vaccine continues. While live, attenuated strains of SIV afford reliable long-term protection in animal models, at least against closely related challenge [...]
Strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type [SIV.sub.mac]239 infection of rhesus macaques by two different vaccine regimens. Six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle SIV (sc51V). Six additional animals were primed with a mixture of cytoplasmic domain-truncated envelope variants of sc51V and boosted with two doses of vesicular stomatitis virus glycoprotein (VSV G) transcomplemented sc51V. While both regimens elicited detectable virus-specific T cell responses, SIV-specific T cell frequencies were more than 10-fold higher after boosting with VSV G trans-complemented sc51V (VSV G sc51V). Broad T cell recognition of multiple viral antigens and Gag-specific [CD4.sup.+] T cell responses were also observed after boosting with VSV G sc51V. With the exception of a single animal in the repeated immunization group, all of the animals became infected following an intravenous challenge with [SIV.sub.mac]239. However, significantly lower viral loads and higher memory [CD4.sup.+] T cell counts were observed in both immunized groups relative to an unvaccinated control group. Indeed, both sc51V immunization regimens resulted in containment of [SIV.sub.mac]239 replication after challenge that was as good as, if not better than, what has been achieved by other non-persisting vaccine vectors that have been evaluated in this challenge model. Nevertheless, the extent of protection afforded by sc51V was not as good as typically conferred by persistent infection with live, attenuated SIV. These observations have potentially important implications to the design of an effective AIDS vaccine, since they suggest that ongoing stimulation of virus-specific immune responses may be essential to achieving the degree of protection afforded by live, attenuated SIV.
Strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type [SIV.sub.mac]239 infection of rhesus macaques by two different vaccine regimens. Six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle SIV (sc51V). Six additional animals were primed with a mixture of cytoplasmic domain-truncated envelope variants of sc51V and boosted with two doses of vesicular stomatitis virus glycoprotein (VSV G) transcomplemented sc51V. While both regimens elicited detectable virus-specific T cell responses, SIV-specific T cell frequencies were more than 10-fold higher after boosting with VSV G trans-complemented sc51V (VSV G sc51V). Broad T cell recognition of multiple viral antigens and Gag-specific [CD4.sup.+] T cell responses were also observed after boosting with VSV G sc51V. With the exception of a single animal in the repeated immunization group, all of the animals became infected following an intravenous challenge with [SIV.sub.mac]239. However, significantly lower viral loads and higher memory [CD4.sup.+] T cell counts were observed in both immunized groups relative to an unvaccinated control group. Indeed, both sc51V immunization regimens resulted in containment of [SIV.sub.mac]239 replication after challenge that was as good as, if not better than, what has been achieved by other non-persisting vaccine vectors that have been evaluated in this challenge model. Nevertheless, the extent of protection afforded by sc51V was not as good as typically conferred by persistent infection with live, attenuated SIV. These observations have potentially important implications to the design of an effective AIDS vaccine, since they suggest that ongoing stimulation of virus-specific immune responses may be essential to achieving the degree of protection afforded by live, attenuated SIV.