Live attenuated rubella vectors express SIV and HIV vaccine antigens, incorporate them into virions, infect rhesus macaques, and elicit high titer antibodies to the insert

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	FDA/CBER	VIROL-17

Authors

• K. Virnik
• Y. Ni
• M. Hockenbury
• I. Berkower

Abstract

Despite the urgent need for HIV vaccines, there have been many obstacles to their development. These include: weak immunogenicity, poor neutralizing activity, and limited durability. We have developed a live attenuated viral vector, based on the rubella vaccine strain to overcome these problems. We have identified two insertion sites in the rubella genome, where foreign antigens such as SIV Gag and HIV MPER can be expressed without affecting viral growth. One site was located in the structural region. At this site, the insert was expressed as part of the structural polyprotein, processed to a free protein, and incorporated into virions. The vectors stably expressed the antigen, while growing to high titer in vitro. The vectors grew well in rhesus macaques, as detected by RT-PCR, until they elicited anti-rubella antibodies. They also elicited high titer antibodies against the SIV Gag insert in all animals. Macaques are the animal model of choice for SIV and SHIV challenge studies. They will allow us to test rubella vectors with different vaccine inserts for growth, immunogenicity, and protection against SIV or SHIV challenge.

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