Expression of interferon-gamma by SIV increases attenuation and vaccine efficacy for juvenile and neonatal rhesus macaques.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Expression of interferon-gamma by SIV increases attenuation and vaccine efficacy for juvenile and neonatal rhesus macaques.

Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:61. Unique Identifier : AIDSLINE MED/97927041
Yilma T; Ahmad S; Jones L; Giavedoni LD; International Laboratory of Molecular Biology for Tropical Disease; Agents, University of California, Davis, CA. Fax: (916) 752-1354.

Abstract: We have developed recombinant SIVs expressing IFN-gamma SIV(HyIFN)) as a novel approach for enhancing the safety and efficacy of live attenuated vaccines for AIDS. Macaques vaccinated with SIV(HyIFN) have reduced pre- and post-challenge virus load compared to those vaccinated with SIV(deltanef).We now report that SIV(HyIFN) administered orally is non-pathogenic for newborn macaques, and induces protective immunity against challenge with virulent SIV. Three neonatal macaques given an oral dose of 2 x 10(5) TCID(50) of SIV(HyIFN) showed no clinical signs of SAIDS. Two of the three macaques had detectable virus in PBMCs only) at one week post-inoculation (WPI). The third animal, 29084, had detectable virus in plasma and PBMCs at 2 weeks post-inoculation and SIV(HyIFN) was sporadically detected after 3 WPI. Analysis of virus load and immune responses over a 9-month period showed that only one macaque (29084) had high titers of antibodies to SIV. After 9 months, orally-inoculated macaques and 3 naive controls were challenged with 10 AID(50) of virulent SIV(mac251) intravenously; all animals except 29084 became infected with challenge virus as determined by PBMCs and lymph node cells co-cultures and PCR. The protected animal had a CD4/CD8 ratio of 1.53 at the 39th week after challenge. These initial studies show that SIV(HyIFN) is non-pathogenic for newborn macaques and low level infection with this novel vaccine is necessary for protection from infection with SIV(mac251).

Keywords: *Interferon Type II/GENETICS *SIV/GENETICS *Viral Vaccines/IMMUNOLOGY
971130
M97B1182

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