Insights into a Phase 1 Trial of a MERS-CoV Vaccine Candidate

Based on findings from a comparative-dose trial with a candidate vaccine, headway is being made in the process toward a MERS prophylaxis.

While the world’s attention has been focused on coronavirus 2019 (COVID-19), there is another coronavirus that we are still working to combat. Middle East respiratory syndrome (MERS) was first identified in 2012 and according to the World Health Organization (WHO), there have been 2494 cases and 858 associated deaths since then.

MERS cases have been identified across 27 countries and caused significant outbreaks in Saudi Arabia and South Korea.

This zoonotic disease is a priority for WHO efforts regarding research and development, meaning that there is an urgent need to develop medical countermeasures. Much of this urgency is not only due to the sporadic nature of outbreaks, but also the observed 30% fatality rate. Researchers have been working for years on a vaccine to help combat MERS, especially for healthcare workers as there are frequently healthcare-associated outbreaks.

A new study focused on a new MERS modified vaccinia virus Ankara (MVA)-based vaccine candidate. This approach utilized a MERS-CoV spike glycoprotein expression in healthy adults and the authors focused on the safety and tolerability of it.

The phase 1 trial was conducted at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany and included 26 healthy men and women aged 18-55 years with no significant health problems. The trial took places between December 2015-June 2018, and exclusionary criteria included previous MVA vaccination.

The investigators noted that for the prime immunisation, patients received low- or high-doses of plaque-forming unit (PFU) MVA-MERS-S intramuscularly.

"A second identical dose was administered intramuscularly as a booster immunisation 28 days after first injection," they explained. "As a control group for immunogenicity analyses, blood samples were drawn at identical study timepoints from 6 healthy adults, who did not receive any injections."

Investigators sought a primary endpoint of safety and tolerability of the 2 dosage levels and reactogenicity after administration, while immunogenicity was observed as a secondary endpoint by ELISA and neutralisation tests. Additionally, T-cell immunity was evaluated by interferon-γ-linked enzyme-linked immune absorbent spot assay.

Studying those 14 in the low-dose group and 12 in the high-dose group, 23 received a second dose of MVA-MERS-S and none had severe or serious adverse events. Investigators noted 71% of the low-dose group experienced a total of 67 vaccine-related adverse events, and 83% of the high-dose group report 111 events.

Adverse events included pain, swelling, and induration for local reactions. Beyond this, adverse events included headaches and fatigue as the most common and tended to resolve within 1-3 days.

Investigatos found that following the booster shot, 75% of the low-dose group and 100% of the high-dose group had seroconversion throughout the study and antibody titers mirror those with MERS-CoV-specific neutralizing antibodies.

Ultimately they concluded that MVA-MERS-S appears to be relatively safe and through a dose-effect relationship: "jomologous prime—boost immunisation induced humoral and cell-mediated responses against MERS-CoV.”

More research is fundamentally required but overall this studied yielded promising results and is encouraging for future MERS-CoV research and development into medical countermeasures.