Vaccine against Middle East respiratory syndrome coronavirus
Authors: Xuejuan Shen, Jamal S M Sabir, David M Irwin, Yongyi Shen
Journal: The Lancet Infectious Diseases (2019)

In The Lancet Infectious Diseases, Kayvon Modjarrad and colleagues1Modjarrad K Roberts CC Mills KT et al.Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial.Lancet Infect Dis. 2019; 19: 1013-1022Summary Full Text Full Text PDF PubMed Scopus (216) Google Scholar reported results of the first in-human clinical trial of the GLS-5300 vaccine candidate against Middle East respiratory syndrome (MERS)coronavirus. The vaccine induced both humoral and cellular MERS coronavirus-specific immune responses. These data suggest that GLS-5300 has potential value in protecting humans from MERS coronavirus infections. However, who should be vaccinated? Epidemiological surveys2WHOWHO MERS global summary and assessment of risk.https://www.who.int/csr/disease/coronavirus_infections/risk-assessment-august-2018.pdf?ua=1Date: 2018Date accessed: September 3, 2019Google Scholar concluded that camel contacts, health-care workers, and patient household contacts are high-risk groups. Therefore, they should be the target groups for the vaccine. However, there are many infection cases for which the source of infection could not be identified. The unpredictability of these infections makes it hard to prevent human infections through vaccination for postexposure prophylaxis. For zoonotic disease prevention and control, one-sided disease prevention (either human or animal) is often inefficient. Severe acute respiratory syndrome (SARS) is a successful precedent for containment of emerging coronaviruses based on elimination of the primary reservoir. Although the pathogens of SARS and MERS are both coronaviruses, two major factors lead to different control results. First, although the number of human SARS cases is greater than for MERS, most were due to a so-called super-spreader strain. By contrast, all clades of MERS coronavirus are shared by camels and humans, indicating that MERS coronavirus can easily spill-over from camels to infect humans.3Sabir JSM Lam TTY Ahmed MMM et al.Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia.Science. 2016; 351: 81-84Crossref PubMed Scopus (310) Google Scholar Second, palm civet, the intermediate amplifying host of SARS coronavirus, is an exotic animal that could easily be controlled by banning wild animal trading. However, the intermediate host of MERS coronavirus (dromedary camel) is an important livestock for the Middle East, with key roles in transportation, food, and fabric (wool); thus, it is impossible to eliminate all camels. To control this disease in camels two possibilities exist: mass slaughtering of infected animals or vaccination. Unfortunately, serological surveys showed a very high prevalence (up to 100%) of MERS coronavirus-neutralising antibodies in dromedary camels.4Reusken CB Haagmans BL Muller MA et al.Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study.Lancet Infect Dis. 2013; 13: 859-866Summary Full Text Full Text PDF PubMed Scopus (572) Google Scholar Therefore, it seems impossible to eliminate this disease by mass slaughtering of positive animals. Vaccination of camels seems to be the only choice, but no licensed vaccine for camels is currently available, although several vaccines are in development.5Haagmans BL van den Brand JMA Raj VS et al.An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels.Science. 2016; 351: 77-81Crossref PubMed Scopus (215) Google Scholar Additionally, GLS-5300 has been reported to also be immunogenic in camels.6Muthumani K Falzarano D Reuschel EL et al.A synthetic consensus anti–spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.Sci Transl Med. 2015; 7301ra132Crossref PubMed Scopus (190) Google Scholar Camels are not used routinely in research and, for most laboratories, it would be hard to attain enough animals and work with them. Moreover, they are too big to study in most biosafety facilities. These limitations restrict vaccination tests in camels. It is increasingly recognised that a One Health approach is needed for effective investigation, prevention, and control of emerging zoonotic diseases. In the context of emerging zoonoses, human and veterinary medicines must work together. The eradication of MERS coronavirus in dromedary camels is the primary condition for the control of this disease in the Arabian Peninsula. If the virus continues to circulate in camels, it might attain new mutations that enable human-to-human transmission, resulting in the generation of super-spreader strains. A comprehensive MERS prevention and control effort should focus not only on a human vaccine but also on camel vaccination. We declare no competing interests. This work was supported by grants from the National Natural Science Foundation of China (number 31822056) and Guangdong Natural Science Funds for Distinguished Young Scholar (number 2014A030306046). Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trialThe GLS-5300 MERS coronavirus vaccine was well tolerated with no vaccine-associated serious adverse events. Immune responses were dose-independent, detected in more than 85% of participants after two vaccinations, and durable through 1 year of follow-up. The data support further development of the GLS-5300 vaccine, including additional studies to test the efficacy of GLS-5300 in a region endemic for MERS coronavirus. Full-Text PDF Vaccine against Middle East respiratory syndrome coronavirusThe phase 1, open-label, single-arm, first-in-human evaluation of the Middle East respiratory syndrome (MERS) coronavirus DNA vaccine by Kayvon Modjarrad and colleagues1 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 vaccines2 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,3 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. Full-Text PDF