Immunogenicity of an adenoviral-based Middle East Respiratory Syndrome coronavirus vaccine in BALB/c mice

Abstract

A new type of coronavirus has been identified as the causative agent underlying Middle East Respiratory Syndrome (MERS). The MERS coronavirus (MERS-CoV) has spread in the Middle East, but cases originating in the Middle East have also occurred in the European Union and the USA. Eight hundred and thirty-seven cases of MERS-CoV infection have been confirmed to date, including 291 deaths. MERS-CoV has infected dromedary camel populations in the Middle East at high rates, representing an immediate source of human infection. The MERS-CoV spike (S) protein, a characteristic structural component of the viral envelope, is considered as a key target of vaccines against coronavirus infection. In an initial attempt to develop a MERS-CoV vaccine to ultimately target dromedary camels, we constructed two recombinant adenoviral vectors encoding the full-length MERS-CoV S protein (Ad5.MERS-S) and the S1 extracellular domain of S protein (Ad5.MERS-S1). BALB/c mice were immunized with both candidate vaccines intramuscularly and boosted three weeks later intranasally. All the vaccinated animals had antibody responses against spike protein, which neutralized MERS-CoV in vitro. These results show that an adenoviral-based vaccine can induce MERS-CoV-specific immune responses in mice and hold promise for the development of a preventive vaccine that targets the animal reservoir, which might be an effective measure to eliminate transmission of MERS-CoV to humans.

Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice

“…A DNA vaccine, which was developed by expressing the synthetic consensus anti-spike protein has shown immunogenicity in mice, nonhuman primates (NHPs) and camels (Muthumani et al, 2015), and another DNA plasmid vaccine that expresses the MERS-CoV S glycoprotein has entered Phase I clinical trials (Clinical Trials.gov, 2016). Additionally, delivery of the S antigen by way of DNA vaccination, nanoparticles, recombinant viral vectors such as modified vaccinia Ankara or adenovirus or RBD-based subunit vaccines have shown immunogenicity and efficacy in mice and/or NHPs against MERS-CoV challenge (Du et al, 2013b;Muthumani et al, 2015;Wang et al, 2015;Coleman et al, 2014;Song et al, 2013;Volz et al, 2015;Kim et al, 2014;Lan et al, 2014Lan et al, , 2015.…”

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

“…Levels of IgG1 and IgG2a, which were similar for both antigens, increased over time and then were boosted to their peak level as they plateaued for 3 weeks postboost. Similarly, the nAb levels doubled after the boost, and they plateaued for 3 weeks . The second group used an Ad41 vector, derived from Ad41 virus that infects humans naturally via the gastrointestinal route, making it a suitable vector to induce mucosal immunity and to allow for oral immunization.…”

Middle East respiratory syndrome: current status and future prospects for vaccine development

“…Reports have indicated that recombinant Ad5 vectors, which encode the full-length or S1 extracellular domain, of MERS-CoV S protein induced MERS-CoV S-specific antibody responses in immunized mice, neutralizing MERS-CoV infection in vitro [14]. Ad5 or Ad41 vectors expressing full-length S protein of MERS-CoV have elicited MERS-CoV-specific antibody responses, neutralizing antibodies and T-cell responses in immunized mice [15].…”