Structure-Based Design of Recombinant Spike Subunit Vaccine for Coronavirus Diseases

Mahmuda Mahmuda, Shofi Al Jannah, Azzania Fibriani, Ratih Asmana Ningrum, Andri Wardiana


The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still surging across the globe and has affected serious problems for both health and the global economy; therefore, the development of a vaccine with good efficacy becomes a must. To tackle the pandemic, numerous sectors of academia, industry, and the government collaborate to develop and investigate potential vaccine platforms. The recombinant subunit vaccine is one of the safest types of vaccine. However, its development has lagged behind other platforms, owing to the need for greater antigen manufacturability and immunogenicity. In this review, we outline several protein engineering strategies carried out in developing the recombinant COVID-19 vaccine, including the fusion of antigens with Fc fragment of human IgG, carrier proteins, trimerization domains, and stabilizing mutations. A systematic literature review was performed to summarize key takeaways from studies on developing recombinant subunit vaccines of SARS-CoV, MERS-CoV, and SARS-CoV-2, highlighting vaccine design and expression system, antigen structure, and in vivo and in vitro results of each protein engineering strategy. Several protein engineering strategies, particularly S protein and RBD, can improve the antigen's stability, manufacturability, and immunogenicity. Finally, novel protein engineering strategies are expected to be further developed to increase the vaccines' overall manufacturing, and the current recombinant vaccine candidates will be further processed into clinical stages to confirm their efficacy against pathogenic human coronaviruses.


COVID-19 vaccine; protein subunit, manufacturability; immunogenicity.

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