Mosaic HIV-1 immunogens delivered via a modified vaccinia Ankara (MVA) vector elicit HIV-1-specific immune responses in healthy, uninfected volunteers, researchers report.

"HIV is a very genetically diverse virus and that diversity is one of the reasons that developing an HIV vaccine has been so challenging," Dr. Stephen R. Walsh from Brigham and Women's Hospital and Harvard Medical School reported. "Mosaic immunogens, which are designed by computers to maximize potential coverage, might help broaden the immune responses induced by a vaccine."

In a first-in-human randomized controlled trial, Dr. Walsh et al. tested a regimen of MVA Mosaic in 15 individuals without prior exposure to an HIV-1 vaccine (group 1) and 10 individuals who had received doses of a prototype HIV-1 vaccine (group 2). All were healthy volunteers at low risk for acquiring HIV by standard criteria.

MVA-mosaic vaccine

The vaccine was safe and generally well tolerated, with no serious adverse events or greater-than-moderate adverse events attributed to vaccination. Eight of 15 group 1 subjects developed HIV-1 Env-specific cellular immune responses following the first vaccination, and 10 developed responses following the second injection.

All eight group 2 subjects had detectable responses to at least one of the Env peptide pools after the first injection, with most experiencing greater responses after the second inoculation.

Similarly, seven subjects in group 1 and four subjects in group 2 had responses to at least one of the Gag peptide pools; and seven group 1 subjects and five group 2 subjects had positive responses to one of the Pol pools after the second injection of MVA Mosaic, the researchers reported in The Journal of Infectious Diseases.

MVA Mosaic consistently induced Env-specific binding antibody responses, and these responses were cross-reactive against Env proteins derived from at least three clades of HIV-1 viruses.

"The MVA-mosaic vaccine is currently being tested as a component of a therapeutic vaccine regimen," Dr. Walsh said. "In that study, people infected with HIV will be vaccinated to see if immunization can increase their HIV-specific immune responses. If this is successful, then perhaps in the future, therapeutic vaccines could be used to help people with HIV better control the virus."

"Another viral vaccine delivery system, called adenovirus serotype 26, has also been tested to deliver these same mosaic immunogens," he said. "That vaccine delivery system has recently advanced to an efficacy trial in sub-Saharan Africa which is currently recruiting women at risk of HIV infection."