6th Conference on Retroviruses and Opportunistic Infections
Chicago, IL - January 31-February 4, 1999
Longitudinal analysis of CTL precursor frequency in rhesus macaques immunized with live attenuated SIVmac239 Δnef and challenged with pathogenic SIVmac251.
Nixon DF, Kakimoto WM, Donahoe SM, Gettie A, Ho DD, Marx P, Connor R; The Aaron Diamond AIDS Research Center, New York, NY.
Live attenuated virus vaccines have been shown to provide protection against challenge with a pathogenic SIV in a primate model. Although the correlates of protection have not been established, protection appears to be associated with length of time between immunization and challenge. 5 out of 8 macaques challenged five or ten weeks after immunization were not protected against infection, whereas 7 out of 8 challenged after 15 or more weeks were protected. Protection did not correlate with the presence of neutralizing antibody responses, therefore, we measured the SIV specific CTL precursor frequency to Env, Gag, Pol and Nef antigens before challenge, around the day of challenge, and after challenge in five rhesus macaques comprising Group "D". This group consisted of one control animal who received no vaccination prior to challenge, and four animals immunized with SIVmac239 Δnef. Animals were challenged with SIVmac251 at 25 weeks after immunization, and the control animal Rh 1516, and one experimental animal Rh 1510 became infected. Rh 1506, 1512 and 1514 were protected. SIV specific CTLp were measured by polyclonal stimulation with concanavalin A, and antigen specific restimulation with paraformaldehyde-fixed autologous H. Papio transformed BCL infected with recombinant vaccinia viruses expressing SIV gene products. No CTL were detected in the unimmunized control animal Rh 1516 prior to challenge, nor in the animal Rh 1510 which was not protected, although a strong env specific CTL response was detected in this animal after infection. Strong SIV specific CTL responses to Env and Gag were detected in 2/3 protected animals prior to challenge. SIV specific CTL responses may be an important component of the protection against infection in SIVmac239 deltanef immunized macaques.
Keywords: AEGIS, Macaca mulatta, SIV, Vaccines, Attenuated, Vaccinia virus, Macaca, Vaccination, Immunization, Animal, analysis, AIDS
