Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

Abstract

Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

How to Inhibit Nuclear Factor-Kappa B Signaling: Lessons from Poxviruses

“…Due to their relatively high recombination rates, the availability of simple recombinant virus construction procedures, the lack of integration into the host genome, and their ability to incorporate >25 kb of foreign DNA, poxviruses are being actively pursued as vectors for gene therapy and for applications in oncolytic virotherapy [8][9][10]. In addition, because poxvirus vectors can stimulate strong humoral and T cell-mediated responses to heterologous antigens, poxviruses are also being applied to the development of vaccines for the treatment of other infectious diseases [11][12][13]. These reasons and the ability of poxviruses to manipulate a wide-range of host processes have made studies of these viruses invaluable in understanding host-pathogen interactions and human disease.…”

Rendezvous with Vaccinia Virus in the Post-smallpox Era: R&D Advances

“…Plentiful studies target arboviruses that are on the rise: dengue virus [161], Zika virus [50,[162][163][164][165], West Nile virus [166], yellow fever virus [167], tick-borne encephalitis virus [168,169], chikungunya virus [163,170], and Crimean-Congo hemorrhagic fever virus [171]. Multiple diseases of high prevalence or fatality rate, especially those with epidemic or pandemic potential garner particular attention, including the following examples: ebolavirus [172][173][174][175], Nipah virus [176], influenza virus [177][178][179][180], respiratory syncytial virus [181,182], Middle East respiratory syndrome coronavirus [183,184], and needless to say, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [158,[185][186][187][188][189][190][191][192][193][194][195]. Several VACV-vectored vaccines have entered clinical trials: HIV-1 [196], tuberculosis [197,198], respiratory syncytial virus [199], influenza A virus…”

SARS-CoV-2 vaccines in advanced clinical trials: Where do we stand?

“…Four out of ten of the VV-based SARS-CoV-2 vaccines that are in Phase III trials are based on NRVV platforms and all use adenoviral vectors [ 48 , 50 , 51 , 192 ]. Other vectors that are in Phase I and preclinical evaluation are gorilla adenovirus, Sendai virus vector, adeno-associated virus vector, modified vaccinia virus Ankara, parainfluenza virus 5, deactivated rabies virus and influenza A virus H1N1 vectors [ 8 , [193] , [194] , [195] , [196] , [197] ]. Replicating viral vector (RVV) Multiple SARS-CoV-2 vaccines are also being developed with attenuated viral vectors that can replicate at the site of immunization and can thus elicit stronger immune responses using relatively small vaccine doses.…”

“…Encouragingly, the grade 3 AEs resolved without any medical intervention within 3–4 days of vaccination. None of the study participants reported any serious AEs within 28 days [ 193 ].…”