Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen

Abstract

The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund’s adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.

An update on Middle East respiratory syndrome: 2 years later

“…Other studies showed similar findings of antigenic property of a rRBD protein of MERS-CoV spike (S) [78,[81][82][83]. Moreover, three adjuvants-alum, IFA, CpG and poly (I:C)-in rRBD subunit vaccines were effective in producing RBD-specific cellular and humoral immune responses [84]. Since the N-terminus RBD of (S) glycoprotein is conserved in currently circulating MERS-CoV strains, this terminus is considered a possible vaccine candidate [85].…”

T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV

“…Further, passive immunotherapy using convalescent phase human plasma is being considered in MERS patients after its success in animal models . However, studies also demonstrate that MERS-CoV S protein-derived vaccines induce specific CD8 þ T-cell and virus-neutralizing antibodies, which could contribute to complete protection against MERS-CoV in animal models (Lan et al, 2014;Volz et al, 2015). Based on the investigations of immune memory against SARS-CoV in follow-up studies of recovered patients (discussed above), T-cell responses can provide robust long-term memory and possess a considerable potential for cross-reactivity with heterotypic coronaviruses.…”

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

“…Soon after the identification of MERS‐CoV, several groups developed vaccines for preclinical testing. Recombinant receptor‐binding domain (rRBD), residues 367 to 606 of MERS‐CoV spike (S) protein, has been expressed and tested in mice as a vaccine . It induced RBD‐specific immunoglobulin G (IgG) antibody when it was tested with various adjuvants such as alum, CpG, P(I:C), or IFA.…”

“…It induced RBD‐specific immunoglobulin G (IgG) antibody when it was tested with various adjuvants such as alum, CpG, P(I:C), or IFA. However, only RBD with alum or with alum and CpG was able to induce nAb . This vaccine was then taken further and tested in Rhesus macaques at 2 different dosages, in 3 homologous vaccinations regimen, with 8‐ and 17‐week intervals.…”