Safety and Immunogenicity of a 2-Dose Heterologous Vaccine Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Nairobi, Kenya - PubMed (original) (raw)

Clinical Trial

Safety and Immunogenicity of a 2-Dose Heterologous Vaccine Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Nairobi, Kenya

Gaudensia Mutua et al. J Infect Dis. 2019.

Abstract

Background: During the 2014 West African Ebola outbreak, Ebola vaccine development was accelerated. The phase 1 VAC52150EBL1003 study was performed to investigate 2-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo in an African population located in a high-altitude setting in Nairobi, Kenya.

Methods: Healthy adult volunteers were randomized to receive one of four 2-dose vaccination schedules. The first vaccination was administered at baseline (Ad26.ZEBOV or MVA-BN-Filo), followed by the second vaccination with the alternate vaccine after either 28 or 56 days. Each schedule had a placebo comparator group. The primary objective was to assess the safety and tolerability of these regimens.

Results: Seventy-two volunteers were randomized into 4 groups of 18 (15 received vaccine, and 3 received placebo). The most frequent solicited systemic adverse event was headache (frequency, 50%, 61%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). The most frequent solicited local AE was injection site pain (frequency, 78%, 63%, and 33% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). No differences in adverse events were observed among the different vaccine regimens. High levels of binding and neutralizing anti-Ebola virus glycoprotein antibodies were induced by all regimens and sustained to day 360 after the first dose.

Conclusions: Two-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo was well tolerated and highly immunogenic against Ebola virus glycoprotein.

Clinical trials registration: NCT02376426.

Keywords: Ad26.ZEBOV; Ebola vaccine; MVA-BN-Filo; heterologous 2-dose; safety and immunogenicity.

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Figures

Figure 1.

VAC52150EBL1003 study design. Ad26, Ad26.ZEBOV; MVA, MVA-BN-Filo; TCID50, 50% tissue culture infectious doses; vp, virus particle.

Figure 2.

Anti–Ebola virus glycoprotein immunoglobulin G binding antibody responses (detected by enzyme-linked immunosorbent assay [ELISA]) binding antibody responses (A) and virus neutralizing antibody (VNA) responses (B) following dose 1 vaccination with Ad26.ZEBOV (Ad26) or MVA-BN-Filo (MVA) and heterologous dose 2 vaccination with MVA or Ad26 on day 29 or day 57, 21 days after dose 2. Data are geometric mean concentration (GMC), for ELISA, and geometric mean 50% inhibitory concentration (IC50), for VNA analysis. Error bars represent 95% confidence intervals. NA, not applicable.

Figure 3.

Durability of anti–Ebola virus glycoprotein immunoglobulin G binding (A) and neutralizing (B) antibody responses following dose 1 vaccination with Ad26.ZEBOV (Ad26) or MVA-BN-Filo (MVA) and heterologous dose 2 vaccination with MVA or Ad26 on day 29 or day 57. Data are geometric mean values; error bars represent 95% confidence intervals. ELISA, enzyme-linked immunosorbent assay; IC50, 50% inhibitory concentration.

Figure 4.

Median CD8+ T-cell responses (A) and CD4+ T-cell responses (B) following first dose vaccination with Ad26.ZEBOV (Ad26) or MVA-BN-Filo (MVA) and heterologous second dose vaccination with MVA or Ad26 on day 29 or day 57.

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References

1. Centers for Disease Control and Prevention (CDC). 2014 Ebola outbreak in West Africa—case counts 2016. https://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html. Accessed April 2018.
1. Lambe T, Bowyer G, Ewer KJ. A review of phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines? Philos Trans R Soc Lond B Biol Sci 2017; 372:20160295. - PMC - PubMed
1. Milligan ID, Gibani MM, Sewell R, et al. . Safety and immunogenicity of novel adenovirus type 26- and modified vaccinia ankara-vectored Ebola vaccines: a randomized clinical trial. JAMA 2016; 315:1610–23. - PubMed
1. Winslow RL, Milligan ID, Voysey M, et al. . Immune responses to novel adenovirus type 26 and modified vaccinia virus ankara-vectored Ebola vaccines at 1 year. JAMA 2017; 317:1075–7. - PubMed
1. Anywaine Z, Whitworth H, Kaleebu P, et al. . Randomized clinical trial examining safety and immunogenicity of heterologous prime-boost Ebola vaccines, Ad26.ZEBOV and MVA-BN-Filo: 12-month data from Uganda and Tanzania. J Infect Dis 2019. In press. - PMC - PubMed

Safety and Immunogenicity of a 2-Dose Heterologous Vaccine Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Nairobi, Kenya - PubMed (original) (raw)