Vaccine against Middle East respiratory syndrome coronavirus.

The phase 1, open-label, single-arm, first-in-human evaluation of the Middle East respiratory syndrome (MERS) coronavirus DNA vaccine by Kayvon Modjarrad and colleagues is an important step forward for achieving one of the WHO R&D Blueprint for MERS aims, which calls for development of two types of human MERS vaccines for long-term protection of people at high exposure risk and for reactive use in outbreak settings. Modjarrad and colleagues' results should be viewed with cautious optimism. Apart from overcoming the operational challenges stated in the accompanying Comment by In-Kyu Yoon and Jerome Kim, advancement of this DNA vaccine to a second phase 1 or 2a trial will need to overcome other operational and logistical challenges and must target those most at risk of succumbing to the disease.

The high mortality and severe disease seen in MERS are positively correlated with age and presence of comorbidities, including chronic liver, kidney, and heart disease, diabetes, and immunosuppressive conditions. Furthermore, host immune responses to MERS coronavirus could contribute to disease severity and outcomes. Thus, vaccine-induced immune responses in populations with these high-risk characteristics could potentially have harmful effects. These barriers were encountered in severe acute respiratory syndrome coronavirus vaccine development over 15 years ago, and might also hold true for MERS coronavirus. Therefore, any MERS coronavirus vaccine must specifically target the most vulnerable populations and assess safety and generation of robust, long-lasting protective immune responses. At week 60, the MERS DNA vaccine induced humoral and cellular responses in only 51 (77%) of 66 participants and 42 (64%) of 66 participants, respectively, and only two (3%) of 66 participants maintained neutralising antibodies until the end of the study. Thus, generation of humoral and cellular immune responses might not equate with long-term protection.

The phase 1 DNA vaccine developed for the US military aptly illustrates that advances in technology, vaccine platforms, clinical trial designs, and bioinformatics, together with serious investment by stakeholders, provide opportunities for rapid vaccine development and evaluation. Countries where MERS is endemic must invest more seriously in both human and camel vaccine development. With the continuing outbreaks of MERS coronavirus 7 years after it was first discovered, effective human vaccines could be the ideal way to prevent spread and evolution of the virus. Logistical issues of the small and sporadic number of new MERS cases at different geographical locations need to be overcome by a more coordinated approach for research, something that needs to be advanced more rapidly than the current pace of research and development. Being a DNA vaccine candidate, the GLS-5300 MERS coronavirus vaccine allowed for rapid design and production and was advanced into the clinic within 9 months of preclinical candidate vaccine selection. The encouraging results of the phase 1 MERS DNA vaccine study should be advanced quickly to include studies with adequate numbers of elderly and comorbid populations, with careful consideration of safety and of the longevity of the protective response, thereby mitigating future outbreaks and alleviating disease burden from the most susceptible populations—elderly people, immunosuppressed people, and health-care workers.