Vaccine and Infectious Disease Division

Early evaluations of a peptide-based HIV vaccine

While some successful vaccines include the entirety of the virus of interest, either in a killed or inactivated form, candidate HIV vaccines generally include only a piece of the virus, for safety reasons.  Either pieces of viral DNA or proteins can be used, although many trials have focused on DNA vaccines.  A study led by Dr. Barney Graham, Chief of the Viral Pathogenesis Laboratory and Clinical Trials Core Laboratory at the National Institute of Allergy and Infectious Diseases, along with VIDD co-director Dr. Julie McElrath and VIDD member Dr. Ann Duerr and colleagues, examined a candidate HIV vaccine using protein pieces, or peptides, from different parts of the HIV Envelope protein and formulated with a potent adjuvant.  These peptides were designed to stimulate immune responses from CD4+ T cells, CD8+ T cells, and antibodies. 

The researchers enrolled 24 volunteers in a small clinical trial designed to address the vaccine’s safety, with a secondary objective to determine vaccine recipients’ immune responses elicited by the vaccine.  Although the vaccine showed no ill effects in animal studies, this trial was stopped early because six of the vaccine recipients developed side effects: four had pain and abscesses at the site of injection, and two had headache, chills, nausea, and myalgia following vaccination.  Although the trial originally planned three injections and participants completed only one or two before it was stopped, the researchers could still assess the immunogenicity elicited by the abbreviated vaccination schedule.  They found that most vaccinees had good antibody responses, and a few showed detectable T cell responses as well.  Future studies using novel adjuvants will have to be carefully designed to avoid such negative side effects.

Graham BS, McElrath MJ, Keefer MC, Rybczyk K, Berger D, Weinhold KJ, Ottinger J, Ferarri G, Montefiori DC, Stablein D, Smith C, Ginsberg R, Eldridge J, Duerr A, Fast P, Haynes BF; AIDS Vaccine Evaluation Group.  Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity.  PLoS One. 2010 Aug 10;5(8):e11995.