Background:  EV02 is a phase I trial evaluating the safety and immunogenicity of 2 DNA and poxvirus-based vaccines expressing HIV genes derived from the Chinese R5 HIV clade C virus (97CN54). The same recombinant HIV DNA, consisting of a gag-pol-nef polyprotein and env, is inserted in the NYVAC-C and DNA-C vaccines.

Methods:  We enrolled 40 volunteers to DNA-C intramuscularly (weeks 0, 4) + NYVAC-C intramuscularly (weeks 20, 24) (n = 23), or NYVAC-C alone (weeks 20, 24) stratified by clinical site (25 in Switzerland and 15 in the United Kingdom). We administered 4 mg of DNA-C (2 mg into each vastus lateralis muscle), and 1 mL of NYVAC-C into the deltoid muscle. The primary safety endpoints were grade 3/4 (severe/extreme) local and systemic events, assessed clinically 10 minutes, 1 hour, and 1 to 7 days after each immunization.

Results:  The treatment groups were not perfectly balanced because of the differential enrolment across the sites with 23 volunteers (11 female) being allocated to DNA-C + NYVAC-C, of whom 21 (10 female) received both DNA immunizations. All participants had completed at least 1 week of follow-up after the second DNA-C vaccination. After the first injection, 2 volunteers discontinued, 1 for a vasovagal (grade 2) reaction and 1 for a rise in ALT (grade 4 down to grade 1 within a week). Pain and erythema were the most frequent local reactions reported in 22 and 17 participants, respectively, at either time-point, and these were mild with only 2 exceptions (moderate pain). Systemic reactions were reported by 12 participants, including malaise (2 of 11 moderate), headache (1 of 9 moderate), myalgia (1 of 6 moderate), nausea, and chills. The pattern was broadly similar at weeks 0 and 4, with a median duration of 1 day (range 1 to 9). Of 35 volunteers, 22 (12 female) have received the first NYVAC-C immunization, and 17 (8 female) have received both and completed at least 1 week of follow-up. Following the first NYVAC-C, 1 participant had erythema and swelling with induration (grade 3). Symptoms were mild, as were local and systemic reactions following the second immunization. Local reactions were more common than systemic ones, reported in 19 and 13 participants, respectively, but the majority were mild (89% of all 114 events; 93% of 75 local events at either immunization) with a median duration of 2 days (range 1 to 8).

Conclusions:  To date, 4-mg DNA-C and NYVAC-C appears to be safe and sufficiently well tolerated. Vaccine-induced HIV-1-specific interferon (IFN)-g-secreting T cells will be assessed by ELISpot.