Development of a SARS Coronavirus Vaccine from Recombinant Spike Protein Plus Delta Inulin Adjuvant

Abstract

Given periodic outbreaks of fatal human infections caused by coronaviruses, development of an optimal coronavirus vaccine platform capable of rapid production is an ongoing priority. This chapter describes the use of an insect cell expression system for rapid production of a recombinant vaccine against severe acute respiratory syndrome coronavirus (SARS). Detailed methods are presented for expression, purification, and release testing of SARS recombinant spike protein antigen, followed by adjuvant formulation and animal testing. The methods herein described for rapid development of a highly protective SARS vaccine are equally suited to rapid development of vaccines against other fatal human coronavirus infections, e.g., the MERS coronavirus.

Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection

“…9 Advax is an adjuvant derived from delta inulin, a polysaccharide found in the roots of plants of the Compositae family. 10,11 Advax adjuvant has shown high levels of efficacy in vaccines against respiratory syncytial virus, 11 West Nile virus and Japanese encephalitis virus, 12,13 influenza, [14][15][16] severe acute respiratory syndrome coronavirus, 17 Listeria, 18 onchocercosis 19 and anthrax, 20 amongst others, consistent with its having broad efficacy across viral, bacterial and parasitic vaccines. An advantage of delta inulin adjuvant is that it enhances both Th1 and Th2 T cell responses.…”

“…We have previously shown that Advax delta inulin adjuvant can be combined with other immunomodulators such as TLR9 agonists (CpG oligonucleotides) 17 or NOD2 agonists (murabutide), 20 to make potent combination adjuvants. In this study we hypothesized that a new adjuvant formulation designated as Advax4 that combined all three individual immunomodulatory agents would when combined with rCMX or a new fusion protein of CMX and ESAT-6 (rECMX) induce potent cellular and humoral immune responses that might better control TB infection.…”

The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS

“…Some researchers believed that there were four inserts in the S protein of 2019-nCoV, which may be the result of artificial modification. The SARS-S has been widely studied, including vaccine development and drug design[42, 43]. The key residues 663-VSLLRSTSQ-671 involved in SARS-S protein cleavage site was missed in all structures that have been resolved to date due to its flexibility.…”

Development of Middle East Respiratory Syndrome Coronavirus vaccines – advances and challenges

“…59,60 Studies of SARS-CoV have identified the S1 subunit, especially the RBD of SARS-CoV as a primary target for NAb in mice, NHPs, and humans. 55,[61][62][63][64][65] Similarly, for MERS-CoV, the full-length or fragments of S protein, particularly the RBD, has been used to demonstrate partial efficacy in rhesus macaques 66,67 as well as inducing NAbs in small animal models such as rabbits and mice. 59,60,[68][69][70][71][72][73] A recent study showed that residues 377-588 of MERS-CoV S protein RBD were capable of eliciting potent humoral and cellular responses, which could be enhanced by adding MF59 adjuvant.…”