ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARSCoV-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. © 2023, International Journal on Advanced Science, Engineering and Information Technology. All Rights Reserved.
ABSTRACT
Immunocompromised patients are susceptible to complications from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The mRNA vaccines BNT162b2 and mRNA-1273 are effective in immunocompetent adults, but have diminished activity in immunocompromised patients. We measured anti-spike SARS-CoV-2 antibody (anti-S) response, avidity, and surrogate neutralizing antibody activity in COVID-19 vaccinated patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Anti-S was induced in 89% of AML and 88% of MDS patients, but median levels were significantly lower than in healthy controls. SARS-CoV-2 antibody avidity and neutralizing activity from AML patients were significantly lower than controls. Antibody avidity was significantly greater in patients after mRNA-1273 versus BNT162b2; there were trends toward higher anti-S levels and greater neutralizing antibody activity after mRNA-1273 vaccination. Patients with AML and MDS are likely to respond to COVID-19 mRNA vaccination, but differences in anti-S levels, avidity, and neutralizing antibody activity may affect clinical outcomes and require further study.
ABSTRACT
INTRODUCTION: COVID-19 vaccine efficacy has been evaluated in large clinical trials and in real-world situation. Although they have proven to be very effective in the general population, little is known about their efficacy in immunocompromised patients. HIV-infected individuals' response to vaccine may vary according to the type of vaccine and their level of immunosuppression. We evaluated immunogenicity of an mRNA anti-SARS CoV-2 vaccine in HIV-positive individuals. METHODS: HIV-positive individuals (n = 121) were recruited from HIV clinics in Montreal and stratified according to their CD4 counts. A control group of 20 health care workers naïve to SARS CoV-2 was used. The participants' Anti-RBD IgG responses were measured by ELISA at baseline and 3-4 weeks after receiving the first dose of an mRNA vaccine). RESULTS: Eleven of 121 participants had anti-COVID-19 antibodies at baseline, and a further 4 had incomplete data for the analysis. Mean anti-RBD IgG responses were similar between the HIV negative control group (n = 20) and the combined HIV+ group (n = 106) (p = 0.72). However, these responses were significantly lower in the group with <250 CD4 cells/mm3. (p < 0.0001). Increasing age was independently associated with decreased immunogenicity. CONCLUSION: HIV-positive individuals with CD4 counts over 250 cells/mm3 have an anti-RBD IgG response similar to the general population. However, HIV-positive individuals with the lowest CD4 counts (<250 cells/mm3) have a weaker response. These data would support the hypothesis that a booster dose might be needed in this subgroup of HIV-positive individuals, depending on their response to the second dose.