The Immune Response Corporation announced the final results of a study at McMaster University Health Sciences Centre suggesting that use of Remune antigen in combination with oligonucleotides containing immunostimulatory CpG motifs (CpG ODN) induces HIV-specific immune responses in genital and vaginal tracts and protected animals from infection after virus challenge. The study was designed to ascertain if this approach might be an effective means of inducing protection and potent immune responses in the genital tract against infection with HIV-1.
"Our results suggest that Remune antigen plus CpG ODN when given as a intranasal immunization can induce significant levels of HIV-specific immunity in the genital tract of mice," said Dr. Kenneth L. Rosenthal, lead investigator of the study at McMaster University Health Sciences Centre in Hamilton, Canada. "Furthermore, these animals were protected from virus challenge in the genital tract. These results suggest that a similar approach should be tested to determine if humans can be protected from sexually transmitted HIV-1 infection through a intranasal immunization."
The study evaluated vaginal and systemic immune responses and protection from vaginal challenge elicited after intranasal immunization of mice with Remune antigen in combination with CpG ODN. Mice immunized with Remune antigen plus CpG ODN had enhanced levels of anti-p24 IgG and IgA antibodies in serum and vaginal washes, and increased production of chemokines and Interferon gamma.
Further the study indicated that intranasal immunization with Remune antigen plus CpG ODN protected mice against intravaginal challenge with a recombinant vaccinia virus expressing HIV-1 gag, suggesting this might be an effective means of inducing potent immune responses in the genital tract and protection against intravaginal infection with HIV-1.
"The use of intranasal immunization represents an innovative method for delivering a potential HIV vaccine into the mucosal system, which is a primary defense mechanism against infection," Dr. Rosenthal said. "It represents significant potential in the ability to more readily administer immunization to large populations."
In addition to McMaster University Health Sciences Center, collaborators included The Immune Response Corporation and Coley Pharmaceutical Group in Ottawa, Canada. The study was conducted under the auspices of the Canadian Network for Vaccines and Immunotherapeutics (CANVAC).
According to a CANVAC statement, CANVAC researchers would use this animal model to test which vaccine preparation or combination of vaccine preparations better protects mice from a genital infection with a recombinant model virus. The vaccine preparations deemed to better protect the mice from infection with the model virus could then be tested in small phase I clinical trials in humans to determine their safety. If successful, the same preparations could be used in larger phase II and III clinical trials both in North America and in Africa to determine their safety and assess if and how well they work.
"In our model, mucosal immunization of the upper airways stimulated mucosal immunity in the genital tract which then was associated with protection from intravaginal virus challenge," Dr. Rosenthal said. "We are now studying whether such immune responses are generated to the different subtypes or clades of HIV found throughout the world, an important question based on the widening HIV epidemic."