Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches


Middle East respiratory syndrome coronavirus (MERS-CoV) is a cause of severe respiratory infection in humans, specifically the elderly and people with comorbidities. The re-emergence of lethal coronaviruses calls for international collaboration to produce coronavirus vaccines, which are still lacking to date. Ongoing efforts to develop MERS-CoV vaccines should consider the different target populations (dromedary camels and humans) and the correlates of protection. Extending on our current knowledge of MERS, vaccination of dromedary camels to induce mucosal immunity could be a promising approach to diminish MERS-CoV transmission to humans. In addition, it is equally important to develop vaccines for humans that induce broader reactivity against various coronaviruses to be prepared for a potential next CoV outbreak.

Immune correlates of protection

A cornerstone for rational vaccine design is defining the determinants of immune protection. Accumulating data from studies done so far on MERS-CoV and other coronaviruses revealed that a combination of both virus-specific humoral and cellular immune responses is required for full protection against coronaviruses. Especially neutralizing antibodies are considered key players in the protective immunity against CoVs. Neutralizing monoclonal antibodies (Mabs) reduced viral loads in MERS-CoV receptor-transduced mice, rabbits and macaques. Similarly, convalescent camel sera increased virus clearance and decreased lung pathological outcomes in mice with an efficacy directly proportional to anti-MERS-CoV-neutralizing antibody (Nab) titers. Also polyclonal sera produced in transchromosomic bovines protected mice against MERS-CoV challenge.

Current MERS-CoV vaccine candidates

Although the MERS-CoV genome encodes for 16 non-structural proteins (nsp1-16) and four structural proteins, the spike (S), envelope (E), membrane (M), and nucleocapsid (N), the viral structural proteins, S and N, show the highest immunogenicity. While both S and N proteins can induce T-cell responses, neutralizing antibodies are almost solely directed against the S protein, with the receptor binding domain (RBD) being the major immunodominant region. Thus, current MERS-CoV vaccine candidates mainly employ the spike protein or (parts of) the gene coding for this glycoprotein.

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