Journal List > J Bacteriol Virol > v.45(4) > 1034198

Lee, Yi, and Inn: Current Advances in the Development of Vaccines and Therapeutic Agents Against MERS-coV

Abstract

Middle East respiratory syndrome (MERS) is an emerging infectious disease caused by the betacoronavirus (MERS-CoV). Since the isolation and identification of MERS-CoV in 2012, cases have been spread to neighboring nations in Arabian Peninsula area and Europe. The recent outbreak of MERS in Korea confirmed that MERS-CoV is capable of causing epidemics through person-to-person transmission. Despite of its high mortality, there is no available effective vaccine and therapeutic agent partly due to its short history. So far, ribavirin and interferon therapy has been failed to prove its efficacy in human patients. Thus, there is an urgent need for the effective countermeasures such as vaccines and therapeutics. In the current review, recent advances in the development of vaccines and therapeutic antibodies have been discussed.

REFERENCES

1). Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev. 2015; 28:465–522.
crossref
2). Cheng VC, Lau SK, Woo PC, Yuen KY. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev. 2007; 20:660–94.
crossref
3). Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012; 367:1814–20.
crossref
4). Gulland A. WHO voices concern over rising numbers of MERS-CoV cases. BMJ. 2014; 348:g2968.
crossref
5). Kupferschmidt K. Emerging diseases. Soaring MERS cases in Saudi Arabia raise alarms. Science. 2014; 344:457–8.
6). Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013; 495:251–4.
crossref
7). He Y, Zhou Y, Siddiqui P, Jiang S. Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry. Biochem Biophys Res Commun. 2004; 325:445–52.
crossref
8). See RH, Zakhartchouk AN, Petric M, Lawrence DJ, Mok CP, Hogan RJ, et al. Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus. J Gen Virol. 2006; 87:641–50.
crossref
9). Almazán F, DeDiego ML, Sola I, Zuñiga S, Nieto-Torres JL, Marquez-Jurado S, et al. Engineering a replication-competent, propagation-defective Middle East respiratory syndrome coronavirus as a vaccine candidate. MBio. 2013; 4:e00650–13.
crossref
10). Yang ZY, Kong WP, Huang Y, Roberts A, Murphy BR, Subbarao K, et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature. 2004; 428:561–4.
crossref
11). Zhao B, Jin NY, Wang RL, Zhang LS, Zhang YJ. Immunization of mice with a DNA vaccine based on severe acute respiratory syndrome coronavirus spike protein fragment 1. Viral Immunol. 2006; 19:518–24.
crossref
12). Muthumani K, Falzarano D, Reuschel EL, Tingey C, Flingai S, Villarreal DO, 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; 7:301ra132.
crossref
13). Weingartl H, Czub M, Czub S, Neufeld J, Marszal P, Gren J, et al. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol. 2004; 78:12672–6.
crossref
14). Lu G, Hu Y, Wang Q, Qi J, Gao F, Li Y, et al. Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature. 2013; 500:227–31.
crossref
15). Mou H, Raj VS, van Kuppeveld FJ, Rottier PJ, Haagmans BL, Bosch BJ. The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies. J Virol. 2013; 87:9379–83.
crossref
16). Du L, Kou Z, Ma C, Tao X, Wang L, Zhao G, et al. A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines. PLoS One. 2013; 8:e81587.
crossref
17). Chen Y, Rajashankar KR, Yang Y, Agnihothram SS, Liu C, Lin YL, et al. Crystal structure of the receptor-binding domain from newly emerged Middle East respiratory syndrome coronavirus. J Virol. 2013; 87:10777–83.
crossref
18). Wang N, Shi X, Jiang L, Zhang S, Wang D, Tong P, et al. Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res. 2013; 23:986–93.
crossref
19). Du L, Zhao G, Kou Z, Ma C, Sun S, Poon VK, et al. Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development. J Virol. 2013; 87:9939–42.
crossref
20). Ma C, Wang L, Tao X, Zhang N, Yang Y, Tseng CT, et al. Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments–the importance of immunofocusing in subunit vaccine design. Vaccine. 2014; 32:6170–6.
crossref
21). Ma C, Li Y, Wang L, Zhao G, Tao X, Tseng CT, et al. Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines. Vaccine. 2014; 32:2100–8.
crossref
22). Coleman CM, Liu YV, Mu H, Taylor JK, Massare M, Flyer DC, et al. Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine. 2014; 32:3169–74.
crossref
23). Bisht H, Roberts A, Vogel L, Bukreyev A, Collins PL, Murphy BR, et al. Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proc Natl Acad Sci U S A. 2004; 101:6641–6.
crossref
24). Gao W, Tamin A, Soloff A, D'Aiuto L, Nwanegbo E, Robbins PD, et al. Effects of a SARS-associated coronavirus vaccine in monkeys. Lancet. 2003; 362:1895–6.
crossref
25). Song F, Fux R, Provacia LB, Volz A, Eickmann M, Becker S, et al. Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies. J Virol. 2013; 87:11950–4.
crossref
26). Kim E, Okada K, Kenniston T, Raj VS, AlHajri MM, Farag EA, et al. Immunogenicity of an adenoviral-based Middle East Respiratory Syndrome coronavirus vaccine in BALB/c mice. Vaccine. 2014; 32:5975–82.
crossref
27). Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP, et al. Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med. 2013; 19:1313–7.
28). Tang XC, Agnihothram SS, Jiao Y, Stanhope J, Graham RL, Peterson EC, et al. Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution. Proc Natl Acad Sci U S A. 2014; 111:E2018–26.
crossref
29). Ying T, Prabakaran P, Du L, Shi W, Feng Y, Wang Y, et al. Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody. Nat Commun. 2015; 6:8223.
crossref
30). Corti D, Zhao J, Pedotti M, Simonelli L, Agnihothram S, Fett C, et al. Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus. Proc Natl Acad Sci U S A. 2015; 112:10473–8.
crossref

Figure 1.
Schematic diagrams for S protein domain structures of SARS-coV and MERS-coV
jbv-45-382f1.tif
Table 1.
Comparison between SARS-CoV and MERS-CoV
  MERS-CoV SARS-CoV
First identification 2012 2003
First identified area Saudi Arabia Southern China
Reservoir Dromedary camel Bats/civets
Transmission Zoonotic Zoonotic
Transmission mode Respiratory droplets/close contact Respiratory droplets/close contact
Latent period 2~15 days 2~14 days
Lineage Lineage C/Betacoronaviridae Lineage B/Betacoronaviridae
Host receptor DPP4 (CD26) ACE2
Infection mode Plasma membrane fusion Endosomal membrane fusion
Fatality >35% ~10%
Detection of neutralizing antibodies Within 12 days after symptoms 5~10 days after symptoms
TOOLS
Similar articles