In a rapid-fire half-hour plenary session, Merck's head of HIV vaccine research Emilio Emini reviewed the company's development program and unveiled the first human immunogenicity data from phase I trials of their DNA and adenovirus type 5 (Ad5) constructs. Currently, both vaccines contain only the gag gene from HIV-1 (clade B) but Merck plans to add nef and pol as the program moves ahead.
Emini outlined the studies that are in progress in both HIV negative and HIV positive volunteers (Merck is also pursuing these vaccines as potential therapeutics).
DNA HIV gag vaccine. The ongoing program involves two doses (1 mg or 5 mg) of gag-expressing DNA in saline or with one of two adjuvants: aluminum phosphate or the experimental nonionic block co-polymer CRL-1005.
Adenovirus 5 (Ad5) HIV gag vaccine. Separate trials are evaluating four escalating doses (108, 109, 1010 and 1011 virus particles or vp) of the gag-expressing Ad5 vector and the final phase of the program (which began in January) is offering recipients of the DNA vaccine an Ad5 booster immunization.
Emini presented data from the separate phase one studies of the DNA and Ad5 candidate vaccines, both conducted in HIV-negative volunteers.
An interesting facet of Merck's vaccine development program involves analyzing the potential of HIV-specific T cells to recognize viruses from multiple clades. Emini reported that the Merck team has looked at T-cell responses in HIV-infected individuals from the US, Brazil, Thailand and Malawi (infected with viruses from clades, A, B and C) and assessed their ability to react against a panel of clade B-derived consensus peptides (comprising the viral proteins gag, pol, nef, rev and tat) in an ELISpot assay. Both the frequency and magnitude of the response to gag, pol and nef was indistinguishable by region, indicating substantial cross-clade reactivity. The proteins rev and tat induced a lower level of T-cell response from all study participants, and individuals from Malawi did not appear to respond to clade B rev and tat at all.
Emini closed his presentation by outlining the results yet to come, which include immunogenicity data from the highest (1011 vp) Ad5 dose and the DNA/Ad5 prime-boost approach in HIV negative volunteers, as well as the safety and immunogenicity information from ongoing trials of these vaccines in HIV-infected individuals. Merck anticipates that these results will become available sometime in the summer of 2002.