Three Ebola Vaccine Regimens Elicit Durable Immune Responses in Adults, Children

An analysis of 3 vaccine regimens for Ebola virus disease showed no safety concerns, and immune responses were observed through 12 months.

Results of a trial that assessed 3 vaccine regimens for Ebola virus disease (EVD) showed no safety concerns, with immune responses observed through month 12. These findings were published in The New England Journal of Medicine.

The partnership for research on Ebola vaccinations (PREVAC) protocol comprised 2 randomized, placebo-controlled trials designed to assess 3 EVD vaccine regimens among adults and children. Adults (age, ³18 years; n=1400) and children (age range, 1-17 years; n=1401) without an EVD history were enrolled at 6 sites across 4 countries in West Africa in 2018. Study participants were randomly assigned to receive either a 0.5-mL dose (5×1010 viral particles) of the Ad26.ZEBOV vaccine followed by a 0.5-mL dose (1×108 infectious units) of the MVA-BN-Filo vaccine at 56 days (Ad26-MVA group; n=396 adults; n=403 children); a 1.0-mL dose (9.4×107 plaque-forming units) of the rVSVΔG-ZEBOV-GP vaccine followed by placebo at 56 days (rVSV group; n=395 adults; n=407 children); 2 rVSVΔG-ZEBOV-GP vaccine doses 56 days apart (rVSV-booster group; n=197 adults; n=202 children); or placebo (n=412 adults; n=389 children).

The primary endpoint was the occurrence of an antibody response at 12 months, defined as immunoglobulin (Ig)G antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU)/mL and at least a 4-fold increase in antibody concentration between baseline and 12 months. Safety and immune responses were evaluated through 12 months.

Among adult participants included in the analysis, the median age was 27 (IQR, 20-38) years, and 45% were women. The children were evenly split in groups on the basis of age, including those aged 1 to 4, 5 to 11, and 12 to 17 years, and 46% were girls.

For adults, 9% of those in the Ad26-MVA group, 22% of those in the pooled rVSV groups, and 5% of those in the placebo group reported an injection-site reaction within the first 7 days after receipt of the first injection. In addition, 50%, 66%, and 44% of adult participants in these groups reported symptoms, respectively. Similar findings were observed after receipt of the second injection.

Further analysis of adult participants showed severe adverse events occurred among 4% of those in the Ad26-MVA group, 2% of those in the rVSV group, 1% of those in the rVSV-booster group, and 1% of those in the placebo group. A total of 6 unrelated deaths occurred.

These two trials provide immunogenicity and safety data for three Zaire Ebola vaccine regimens in adults and in children 1 year of age or older.

At 12 months, 41% of adults in the Ad26-MVA group had an antibody response, with a geometric mean concentration (GMC) of 401 EU/mL. Antibody responses were also observed among 76% adult participants in the rVSV group (GMC, 992 EU/mL), 81% of those in the rVSV-booster group (GMC, 1037 EU/mL), and 3% of those in the placebo group (GMC, 93 EU/mL). Compared with antibody responses among adults who received placebo, responses among adults in all 3 vaccine groups were significant (all P <.001). Of adults in the Ad26-MVA and rVSV-booster cohorts, the greatest response was observed at day 63, or 7 days after receipt of the second injection.

For children, 15% of those in the Ad26-MVA group, 21% of those in the pooled rVSV groups, and 5% of those placebo group reported an injection-site reaction within the first 7 days after receipt of the first injection. In addition, 48%, 60%, and 43% of the children in these groups reported symptoms, respectively. Among all children, the occurrence of severe adverse events was rare (£2%), and there were 5 unrelated deaths.

The researchers evaluated antibody responses among the children at 12 months. Antibody responses were observed among 78% of participants in the Ad26-MVA group (GMC, 828 EU/mL), 87% of those in the rVSV group (GMC, 1415 EU/mL), 93% of those in the rVSV-booster group (GMC, 1745 EU/mL), and 4% of those in the placebo group (GMC, 67 EU/mL). Similar to adult participants, antibody responses significantly differed between children in the placebo vs those in the vaccine groups (all P <.001), and the greatest response among active second dose recipients was also observed at day 63.

The major limitation of this study was the inability to evaluate protection against EVD infection or determine a correlate of protection.

“These two trials provide immunogenicity and safety data for three Zaire Ebola vaccine regimens in adults and in children 1 year of age or older,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.

References:

PREVAC Study Team. Randomized trial of vaccines for Zaire Ebola virus disease. N Engl J Med. 2022;387(26):2411-2424. doi:10.1056/NEJMoa2200072