Two-Vaccine Regimen Yields Best Antibody Response To Ebola

Sequential administration of two different Ebola vaccines spaced several weeks apart yields the best antibody responses, according to an early trial.

Dr. Neil Goldstein of Janssen Infectious Diseases and Vaccines, in Leiden, the Netherlands, and colleagues investigated the safety and immunogenicity of various heterologous and homologous two-dose vaccine regimens targeting Ebolavirus. The regimens included the adenovirus serotype 26 viral vector encoding Zaire glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara (MVA) viral vector encoding the glycoproteins (GPs) from Zaire and Sudan Ebolaviruses and Marburg virus and Tai Forest Ebolavirus nucleoprotein (MVA-BN-Filo), with different dosages, sequences, and intervals of Ad26 and MVA vaccines.

"Janssen conducted this exploratory Phase 1 research in 2015-2017, and the results were previously shared at the European Congress of Clinical Microbiology and Infectious Diseases conference in April 2019," Caitlin Wheeler of Janssen told Reuters Health by email. "This trial was part of a series of early-stage studies to investigate different dosing configurations of our Ebola vaccine regimen and to help identify the optimal regimen."

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All regimens demonstrated acceptable safety profiles, with no deaths, serious adverse events, or adverse events leading to discontinuation. The most frequent local adverse event was injection-site pain, and the most frequent systemic adverse events were headache, fatigue and myalgia.

All two-dose heterologous vaccination regimens induced humoral and cellular immune responses, regardless of vaccine and dose levels. Homologous regimens were less immunogenic, especially the MVA regimen.

Twenty-one days after dose 2, the highest GP-specific IgG-binding antibody responses were obtained with MVA followed by Ad26 (MVA,Ad26) 56 days later, the researchers report in the Journal of Infectious Diseases.

Somewhat lower responses were achieved with 28-day intervals between doses, irrespective of the heterologous vaccination sequence.

Binding antibody responses persisted up to day 360 in 93% of the MVA,Ad26 28-day interval group, in 87% of the MVA,Ad26 56-day interval group, and in 100% of participants in the other heterologous vaccination groups.

Similarly, at 21 days after dose 2, 100% of the MVA,Ad26 56-day interval and high-dose Ad26,MVA groups had neutralizing antibody responses. Responses persisted at day 360 in all MVA,Ad26 14-day- and 28-day-interval participants, while persistence rates in the other groups ranged from 80% to 87%.

All heterologous regimens induced CD4+ and CD8+ T-cell responses.

"Ultimately, the optimal vaccine regimen identified through the global clinical program was the 2-dose regimen approved by the European Commission on July 1, 2020: Zabdeno(r) (Ad26.ZEBOV) followed by Mvabea(r) (BN-MVA-Filo) administered approximately eight weeks later," Wheeler said.

She added, "We are now in the process of working with the World Health Organization on the vaccine prequalification process. Of note, the Zabdeno/Mvabea regimen has already been deployed in the Democratic Republic of the Congo (DRC) and neighboring Rwanda, in response to the 2018-2020 Ebola North Kivu outbreak in the DRC."

Dr. Chad E. Mire of the University of Texas Medical Branch, in Galveston, who has researched various aspects of Ebolavirus and Ebolavirus vaccines, told Reuters Health by email, "Clinically, the vaccines and each regimen appear to be safe and well tolerated by the participants with minimal adverse events reported."

"The clinical trial has low numbers in each of the groups preventing any statistical analysis of the data, so there is nothing that could be stated as significantly different," he said.

"However," he added, "the trend I found most interesting in this clinical trial was that there was no apparent difference between a seven-day and 14-day interval for the prime-boost regimen (MVA,Ad26) comparing antibody titers to the EBOV GP and neutralizing titers of antibodies targeting EBOV GP, whereas the standard 28-day interval for prime-boost produced higher antibody and neutralizing titers to EBOV GP compared to the 14-day interval."

—Will Boggs MD

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