DNA vaccine protects non-human primates against MERS, study shows

A synthetic DNA vaccine candidate for Middle East respiratory syndrome coronavirus (MERS-CoV) developed at The Wistar Institute, US, induced potent immune responses and afforded protective efficacy in non-human primate (NHP) models when given intradermally in abbreviated, low-dose immunisation regimen. 

“While several vaccine products are being advanced against MERS and other coronaviruses, low-dose delivery and shortened regimes are crucial to rapidly induce protective immunity, particularly during emerging outbreaks, as the current SARS-CoV-2 pandemic has emphasised,” said Dr David Weiner, who led the study.

Researchers evaluated the immunogenicity and protective efficacy of their MERS synthetic vaccine when delivered intradermally using a shortened two-dose immunisation schedule compared with intramuscular delivery of higher doses in NHP.

“Given that human efficacy trials for MERS vaccines may be challenging due to the low number of yearly cases, animal models such as our NHP model are valuable as a bridge with human data coming from early-phase clinical trials,” said Weiner.

The team report robust neutralising antibodies and cellular immune responses in all conditions tested. A rigorous virus challenge experiment showed that all vaccination groups were protected against MERS-CoV compared to unvaccinated control animals. However, the low-dose regimen with intradermal delivery was more impactful in controlling disease and symptoms than the higher dose delivered intramuscularly in NHP models.

“To our knowledge, this is the first demonstration of protection with an intradermally delivered coronavirus vaccine,” said Dr Ami Patel, one of the lead authors of the paper. “Intradermal delivery of synthetic DNA vaccines has significant advantages for rapid clinical development. It can be dose sparing and has higher tolerability in people compared with intramuscular injection. The positive results of this study are important not only for the advancement of this MERS vaccine but also for development of other vaccines.”

“Our team is also advancing a COVID-19 vaccine through clinical trials and we were able to do so in a very short time thanks to our previous experience developing the MERS vaccine,” added Weiner.

No evidence of adverse effects on the lungs was observed in any of the dosing groups compared to unimmunised control animals. Through the assessment of a large panel of blood cytokines, researchers showed significant decrease in all mediators of inflammation, which further suggests the vaccine prevents the destructive inflammation induced by coronaviruses.

“In the past 20 years, three new coronaviruses have emerged and caused human outbreaks. The current SARS-CoV-2 pandemic has further emphasised the importance of rapid infection control for coronaviruses and other emerging infectious diseases,” said Dr Emma Reuschel, co-first author on the study. “Vaccine candidates that are simple to deliver, well tolerated and can be readily deployed in resource-limited settings will be important to achieve control of infection.”

The results were published in JCI Insight.