AEGiS-11IAC: Immunization with SIVmne envelope (gp160) vaccines protected macaques against intrarectal challenge by uncloned virus.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Immunization with SIVmne envelope (gp160) vaccines protected macaques against intrarectal challenge by uncloned virus.

Int Conf AIDS 1996 Jul 7-12; 11:4 (abstract no. Mo.A.103)
Polacino P, Stallard V, Klaniecki J, Brown C, Watanabe R, Morton WR, Benveniste RE, Hu SL; University of Washington, Seattle, WA, USA.

OBJECTIVE: Envelope (gp160)-based vaccines, when used in a live virus priming and subunit protein boosting regimen, protected macaques from intravenous and intrarectal challenge by a cloned homologous virus SIVmne E11S. In the present study, we investigated the breadth of the protective immunity elicited by the envelope antigen against intrarectal challenge with uncloned SIVmne.

METHODS: Six Macaca fascicularis immunized with envelope (gp160), were previously challenged and protected from cloned E11S infection. They were boosted again with gp160 and rechallenged intrarectally with 2-20 animal infectious doses of uncloned SIVmne. Six naive animals were included as controls. Infection was monitored by nested-set PCR, PBMC co-culture, viral load by semiquantitative PCR, plasma viremia, and in situ hibridization (ISH). Lymphocyte subset, and SIV-specific antibodies titers were also determined.

RESULTS: PCR analysis of PBMC DNA showed that all 6 control animals became infected after challenge with the uncloned virus while 5/6 of the immunized animals were protected. ISH and DNA PCR analyses showed virus-positive lymph nodes in all six controls starting at week 2. Plasma viremia was transiently detected in some of the control animals. All controls seroconverted after the challenge. The 5 immunized and protected animals remained PCR negative and did not show any sign of infection in their lymph nodes. SIV-specific IgG was detected on day of challenge (DOC) in mucosal secretions of immunized animals examined. The only immunized animal that became infected had the lowest serum antibody titer at DOC as measured by ELISA. An anamnestic response was observed in this animal, indicating the presence of viral replication.

CONCLUSIONS: Envelope (gp160)-based vaccines protected macaques against intrarectal challenge by cloned and uncloned SIVmne, indicating that protection against mucosal infection is achievable by systemic immunizations. Our result also indicates that protection may be more easily achieved against mucosal, rather than blood-borne infections, since the same regimen protected against infection by the cloned virus, but not the uncloned virus, by intravenous inoculations.

Keywords: AEGIS, SIV, Macaca, Immunization, SAIDS Vaccines, Vaccines, Macaca fascicularis, Viral Vaccines, Vaccines, Synthetic, Vaccination, Naphthalenes, Vaccines, DNA, Immunity, protect, Animal, immunology, ICA11

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MoA103