Zaire Ebola Vaccines Produce Antibody Responses as Early as 14 Days

Three vaccine regimens for Zaire Ebola virus disease (EVD) produced antibody responses in adults and children, according to the results of two randomized trials conducted in West Africa.

At 12 months, 41% of adults and 78% of children had a response to the Ad26-MVA regimen (Ad26.ZEBOV followed by MVA-BN-Filo 56 days later), 76% and 87% had a response to the rVSV regimen (rVSVΔG-ZEBOVGP followed by placebo), and 81% and 93% had a response to the rVSV-booster regimen (rVSVΔG-ZEBOVGP with another dose 56 days later) compared with 3% and 4%, respectively, in the placebo group (P<0.001 for all comparisons vs placebo), reported researchers from the PREVAC Study Team.

"Immune responses were elicited by 14 days after injection for these vaccine regimens and were maintained for 12 months," the authors wrote in the New England Journal of Medicine.

They noted that the peak proportion of participants with a response was observed at 3 months (28 days after the receipt of the second dose) in the Ad26-MVA group among both adults and children, at day 28 in the rVSV group for both, and at day 63 among adults and at 3 months among children in the rVSV-booster group.

Although these results add to the evidence for immunogenicity and safety of the Ad26-MVA regimen and the rVSVΔG-ZEBOVGP vaccine in adults and children, "there is no universally agreed-on correlate of protective immunity to EVD, and in this trial we were unable to assess protection from disease given that there were no incident cases of EVD," the team wrote.

"However, it has been shown that levels of glycoprotein-binding antibodies strongly correlate with neutralizing antibody titers in nonhuman primates and humans," they added. "Consequently, an analysis that is based on immunogenicity data such as the one reported here is useful in the evaluation of vaccination strategies against EVD."

Knowing that a response occurs at 14 days is important, they noted, since vaccines are often distributed only when Ebola outbreaks occur. "Given that vaccines against EVD have typically been administered during an outbreak to populations at risk for infection, it was important to investigate the early kinetics of the antibody response."

To this end, "both the rVSV∆G-ZEBOVGP and Ad26.ZEBOV vaccinations led to an increase in geometric mean antibody concentrations beginning at day 14," they wrote.

The Zaire EVD was first recognized in March 2014 in Guinea and spread to Liberia and Sierra Leone, leading to 11,000 deaths across these countries.

Although transmission of Ebola virus to humans is not fully understood, it is thought to occur by exposure to infected animals and spread human-to-human from direct contact with blood or other bodily fluids, as well as indirect contact with environments contaminated by these fluids.

The researchers used the PREVAC protocol, which compared the three vaccine regimens with placebo in adults and children separately. The studies were performed at six sites in four West African countries.

Participants were followed up to assess antibody response, reactions, and symptoms on days 7, 14, and 28 after dose 1. Participants were given dose 2 on day 56, and were further followed at day 63 and during months 3, 6, and 12.

Most injection-site reactions and symptoms, largely grade 1 in severity, were reported during the first week after vaccination.

Among adults, serious adverse events were reported in 4% of the Ad26-MVA group, 2% of the rVSV group, and 1% of the rVSV-booster group and the placebo group. Although six adults died, none were considered related to the vaccine or placebo.

In children, serious adverse events were reported in 1% of the Ad26-MVA group, 2% of the rVSV group and the placebo group, and 1% of the rVSV-booster group. Five children died, with all deaths unrelated to the vaccine or placebo.

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