Ebola Vax Seems to Work in Kids, Too

NATIONAL HARBOR, Md. — An experimental two-dose vaccine regimen against Ebola was safe and produced immune responses in children and adolescents, a researcher said here.

The adenovirus 26 vectored glycoprotein/MVA-BN-Filo (Ad26.ZEBOV/MVA-BN) vaccine regimen, a heterologous two-dose regimen, produced immune responses for up to 12 months following vaccination, and was safe in pediatric cohorts consisting of young children and adolescents, reported Muhammed Afolabi, MD, PhD, of the London School of Hygiene & Tropical Medicine at a presentation at the annual meeting of the American Society of Tropical Medicine & Hygiene.

This is the second Ebola vaccine regimen to be tested in the current ongoing outbreak in the Democratic Republic of the Congo. Previously, the World Health Organization designated this vaccine regimen as the second vaccine to be used in the outbreak. Merck’s rVSV-ZEBOV-GP vaccine was used in the ring vaccination strategy in the DRC, and was recently approved by the European Medicines Association.

Phase I trials of the Ad26.ZEBOV/MVA-BN vaccine regimen were published earlier in 2019. The regimen was shown to be safe and immunogenic in healthy adult volunteers, but no data had been published on children. Afolabi noted that the ongoing Ebola outbreak has a higher case fatality rate in children compared to adults (30%-70%), with 893 children in the current outbreak with Ebola, or 29% of total cases. Of these cases, 40% are in children under age 5, which have a case fatality rate of 77% (compared with 57% in older children), he noted.

Researchers examined the safety and immune responses of the vaccine regimen in a phase II study (EBL2002) and a Phase III study (EBL3001), which used the MenACWY vaccine as an active control. Data from EBL2002 was comprised of two schedules — either a 28-day interval or a 56-day interval for the two doses. EBL3001 used a 56 day interval for the regimen.

Overall, 131 adolescents (ages 12-17) and 132 children (ages 4-11) were randomized 5:1 to vaccine or active placebo in EBL2002; 191 adolescents, 192 children and 192 toddlers (ages 1-3) were randomized 5:1 to vaccine or placebo in EBL3001.

Safety was a primary outcome, and most adverse events (AEs) were mild, with a less than 4% frequency of grade 3 solicited AEs across the vaccine cohorts in EBL2002. Fever was more commonly reported in children compared to adolescents in the vaccine group (22.2%-27.8% vs less than 10%, respectively). Adolescents had higher frequency of grade 3 unsolicited AEs than children (10.9%-18.2% vs 0-5.6%, respectively). There were no severe AEs related to the vaccine in any cohort, the authors noted.

Results were similar in EBL3001, though researchers found a higher frequency of unsolicited AEs in toddlers versus children and adolescents, with all but one in the placebo group unrelated to the vaccine. There was one adolescent and one toddler death unrelated to the study.

Examining immune responses, all children and adolescents in EBL2002 responded to the vaccine after the second dose, and a year later, these responses persisted in 96%-98% of children and 90%-92% of adolescents. They noted slightly higher responses for the 56-day interval schedule compared to the 28-day schedule.

For EBL3001, there were 98%-99% responders following the second dose of vaccine. Researchers noted an overall trend of higher geometric mean antibody concentration in toddlers compared to children and adolescents. At 12 months after dose 1, responses were observed in 70%-96% of children, toddlers and adolescents, they said.

More Promising News for Adults

A second study featured data from EBL2002 that examined responses to the vaccine among adults and adults living with HIV. Houreratou Barry, MD, of the University of Nairobi in Kenya, presented data from 668 healthy adults and 142 adults living with HIV. Similar to the phase I data, the phase II data found a low frequency of grade 3 systemic AEs, with the most frequent solicited systemic AEs being fatigue, headache and myalgia, or muscle pain.

Following the second vaccine, there were 100% responders among adults living with HIV, and 86% to 88% were responders a year later. In healthy adults, at least 78% showed binding antibody responses a year after dose 1. The researchers also noted that binding antibody levels were similar between HIV-infected and healthy adults.