Utility of the Sindbis replicon system as an Env-targeted HIV vaccine.

Abstract:

:Sindbis replicon-based vaccine vectors are designed to combine the immunostimulatory properties of replicating viruses with the superior safety profile of non-replicating systems. In this study we performed a detailed assessment of Sindbis (SIN) replicon vectors expressing HIV-1 envelope protein (Env) for the induction of cell-mediated and humoral immune responses in a small animal model. SIN-derived virus-like particles (VLP) elicited Env-specific antibody responses that were detectable after boosting with recombinant Env protein. This priming effect could be mediated by replicon activity alone but may be enhanced by Env attached to the surface of VLP, offering a potential advantage for this mode of replicon delivery for Env based vaccination strategies. In contrast, the Env-specific CTL responses that were elicited by SIN-VLP were entirely dependent on replicon activity. SIN-VLP priming induced more durable humoral responses than immunization with protein only. This is important from a vaccine perspective, given the intrinsic tendency of Env to induce short-lived antibody responses in the context of vaccination or infection. These results indicate that further efforts to enhance the magnitude and durability of the HIV-1 Env-specific immune responses generated by Sindbis vectors, either alone or as part of prime-boost regimens, are justified.

journal_name

Vaccine

journal_title

Vaccine

authors

Center RJ,Miller A,Wheatley AK,Campbell SM,Siebentritt C,Purcell DF

doi

10.1016/j.vaccine.2013.02.064

subject

Has Abstract

pub_date

2013-04-26 00:00:00

pages

2260-6

issue

18

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(13)00253-3

journal_volume

31

pub_type

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