The use of the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein of the Mayinga variant (Ad26.ZEBOV) as a booster for children who previously received 2 doses of the Ad26.ZEBOV vaccine and a modified vaccinia Ankara (MVA) vaccine is a safe and immunogenic vaccine regimen for Ebola virus disease (EBV). These study results were published in The Lancet Infectious Diseases.
Researchers conducted an open-label, non-randomized phase 2 trial at a single clinic in Kambia Town, Sierra Leone. Included participants were children who received an AD26.ZEBOV booster 3 years after receipt of the first dose of the initial vaccine regimen. The initial vaccine regimen included 2-doses of the AD26.ZEBOV vaccine followed by 1 dose of MVA-BN-Filo, a vector-based vaccine encoding glycoproteins from Ebola (Mayinga), Sudan (Gulu), and Marburg (Musoke) viral variants, as well as the nucleoprotein from the Tai Forest virus; the vaccines were administered 56 days apart. Participants were observed for 28 days following booster vaccination. The primary outcomes were the safety and immunogenicity of a booster dose of the AD26.ZEBOV vaccine for protection against EBV. The researchers used linear regression for geometric mean concentrations (GMCs) and P-values were calculated with t-testing.
The final analysis included 50 healthy children in 2 cohorts divided by age. The first cohort had 27 (54%) participants (median age, 5 [IQR, 4-5] years; 30% female) and the second cohort had 23 (46%) participants (median age, 13 [IQR, 11-14] years; 48% female). A convenience sample was used.
Following receipt of the AD26.ZEBOV vaccine booster, no severe adverse events (AEs) occurred among the participants. Solicited AEs occurred in 18 participants, of whom 8 (30%) were in the first cohort and 10 (43%) were in the second cohort. All solicited AEs were short (≤3 days) and of mild severity, with injection site pain as the most common event.The most common unsolicited AE was malaria, occurring among 19 (70%) and 6 (26%) participants in the first cohort and second cohorts, respectively.
Immunogenicity was robust. Seven days after booster vaccination, the Ebola virus glycoprotein-specific immunoglobulin (Ig)G binding antibody GMC among all participants was 28,561 (95% CI, 20,255-40,272) enzyme-linked immunosorbent assay (ELISA) U/mL, 44-times higher than before receipt of the booster. At 21 days after booster vaccination, the GMC of Ebola virus glycoprotein-specific IgG binding antibodies increased to 64,690 (95% CI, 48,356–86,541) ELISA U/mL, 101-times higher than before receipt of the booster.
Limitations of this study include the inability to assess cellular immune responses and the inability to determine if concentrations of binding antibodies induced by booster vaccination indicate protection against EBV. The study’s time frame also did not allow the researchers to assess for neutralizing antibodies against EBV or for AEs that may have occurred after the 28-day follow-up period.
According to the researchers, “Ebola virus disease affects children in many different ways: young children (aged <5 years) have a more rapid disease progression and a higher risk of dying than adults.”
Disclosure: Some authors declared affiliations with the pharmaceutical industry, and this research was supported by Janssen Vaccines and Prevention. Please see the original reference for a full list of disclosures.
Manno D, Bangura A, Baiden F, et al. Safety and immunogenicity of an AD26.ZEBOV booster dose in children previously vaccinated with the two-dose heterologous Ad26.ZEBOV and MVA-BN-filo ebola vaccine regimen: an open-label, non-randomised, phase 2 trial. Lancet Infect Dis. Published online October 20, 2022. doi:10.1016/s1473-3099(22)00594-1