Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

Timothy M. Uyeki; Karl J. Erlandson; George Korch; Michael O'Hara; Michael Wathen; Jean Hu-Primmer; Sally Hojvat; Erik J. Stemmy; Armen Donabedian

Disclosures

Emerging Infectious Diseases. 2016;22(7):e1-e11. 

In This Article

Vaccines

Human Vaccination

Development of MERS-CoV candidate vaccines was initiated by the National Institute for Allergy and Infectious Diseases at the National Institutes of Health, academic investigators, and several companies (Table 5). Most candidate vaccines are still being evaluated in animal models. They have generally targeted the spike protein of MERS-CoV and are recombinant virus, subunit, DNA, or virus-like vector vaccines.[60,63–67] One live-attenuated MERS-CoV candidate vaccine is in early development.[66] Preliminary studies for several other MERS-CoV vaccine candidates have been initiated, and early results demonstrate immunogenicity; 2 have progressed to NHP challenge, and a phase 1 clinical study in adults of 3 different doses of a DNA plasmid vaccine that expresses the MERS-CoV spike protein was started in January 2016.[61] Ongoing assessment of antigenic evolution of circulating MERS-CoV strains is essential for informing vaccine development.[68]

A concern that must be addressed in the development of MERS-CoV vaccines is the potential for causing antibody-dependent enhancement of disease upon virus challenge, such as what was observed with a SARS-CoV candidate vaccine upon SARS-CoV challenge.[69] The lack of a precedent of coronavirus vaccines for humans poses another challenge for the evaluation of MERS-CoV vaccines for humans, although vaccines against other animal coronaviruses are safe and in use in animals.

Camel Vaccination

Considering the cultural importance of dromedaries on the Arabian Peninsula for meat, milk, and racing, prevention of camel-to-camel MERS-CoV transmission and reduction of spread from dromedaries to humans by camel vaccination is being investigated by government, academic, and commercial investigators (Table 6). Young camels appear to be at high risk for MERS-CoV infection and could be a priority group for vaccination;[73,74] the loss of maternal MERS-CoV antibodies ≈5–6 months after birth suggests a short time window for vaccination.[75] A major challenge to this approach is that dromedaries can be reinfected with MERS-CoV; a study by Farag et al. found no correlation between MERS-CoV RNA levels and neutralizing antibodies in camels,[76] suggesting that antibodies may not be protective against infection. Because older camels can be reinfected, a camel vaccination strategy may require multiple dosing and booster vaccination to increase effectiveness over time. Experimental MERS-CoV infection studies and vaccine studies of a small number of dromedaries have been conducted in large animal Biosafety Level 3 facilities in the United States and overseas.[19] In addition, 3 doses of a DNA vaccine containing the MERS-CoV spike protein induced humoral immunity in dromedaries.[60] In a recent study, a modified vaccinia virus Ankara vaccine that expresses the MERS-CoV spike protein was administered intranasally and intramuscularly to dromedaries; when challenged intranasally with MERS-CoV, vaccinated dromedaries had fewer signs of respiratory infection and lower MERS-CoV titers in the upper respiratory tract compared with unvaccinated dromedaries.[77] Alpacas (New World camelids) are being investigated as a suitable proxy for camels because of the lack of available dromedaries in the United States, the high cost of acquiring dromedaries, and the relatively smaller size of alpacas.[26,27]

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