Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2

Stewart-Jones, Guillaume B. E.; Elbashir, Sayda M.; Wu, Kai; Lee, Diana; Renzi, Isabella; Ying, Baoling; Koch, Matthew; Sein, Caralyn E.; Choi, Angela; Whitener, Bradley; Garcia-Dominguez, Dario; Henry, Carole; Woods, Angela; Ma, LingZhi; Montes Berrueta, Daniela; Avena, Laura E.; Quinones, Julian; Falcone, Samantha; Hsiao, Chiaowen J.; Scheaffer, Suzanne M.; Thackray, Larissa B.; White, Phil; Diamond, Michael S.; Edwards, Darin K.; Carfi, Andrea

doi:10.1126/scitranslmed.adf4100

Cited by 9 publications

(2 citation statements)

References 48 publications

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“…Once inside, mRNA is released, leading to spike protein translation in ribosomes. The final steps involve spike protein secretion, internalization by APCs, and incorporation into the major histocompatibility complex (MHC) class II antigen-presenting complex [ 31 ]. This process generates an adaptive immune response, fostering antibody and cell-mediated immunity against SARS-CoV-2 spike proteins [ 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

The Epidemiology of COVID-19 Vaccine-Induced Myocarditis

Costa,

Moniati

2024

Advances in Medicine

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Background. In December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the COVID-19 pandemic, with millions of deaths worldwide. Vaccine breakthroughs in late 2020 resulted in the authorization of COVID-19 vaccines. While these vaccines have demonstrated efficacy, evidence from vaccine safety monitoring systems around the globe supported a causal association between COVID-19 vaccines, in particular those using mRNA technology, i.e., Moderna’s mRNA-1273 and Pfizer-BioNTech’s BNT162b2, and myocarditis. Objective. This paper aims to investigate the epidemiology of mRNA COVID-19 vaccine-induced myocarditis, including age, ethnicity, and gender associations with these vaccines. It also discusses the immunopathophysiological mechanisms of mRNA COVID-19 vaccine-associated myocarditis and outlines principles of diagnosis, clinical presentation, and management. Methods. A literature review was conducted using PubMed, Embase, and Queen Mary University of London Library Services databases. Search terms included “myocarditis,” “coronavirus disease 2019,” “SARS-CoV-2,” “mRNA Covid-19 vaccines,” “Covid vaccine-associated myocarditis,” “epidemiology,” “potential mechanisms,” “myocarditis diagnosis,” and “myocarditis management.” Results. While the definite mechanism of mRNA COVID-19 vaccine-associated myocarditis remains ambiguous, potential mechanisms include molecular mimicry of spike proteins and activation of the adaptive immune response with dysregulated cytokine expression. Male predominance in COVID-19 vaccine-induced myocarditis may be attributed to sex hormones, variations in inflammatory reactions, coagulation states based on gender, and female-specific protective factors. Moreover, an analysis of diagnostic and management strategies reveals a lack of consensus on acute patient presentation management. Conclusion. In contrast to viral infections that stand as the predominant etiological factor for myocarditis with more severe consequences, the mRNA COVID-19 vaccination elicits a mild and self-limiting manifestation of the condition. There is currently insufficient evidence to confirm the definite underlying mechanism of COVID-19 vaccine-associated myocarditis. Further research is needed to develop preventive and therapeutic solutions in this context.

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Section: Introductionmentioning

confidence: 99%

The Epidemiology of COVID-19 Vaccine-Induced Myocarditis

Costa,

Moniati

2024

Advances in Medicine

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“…Generally, mRNA vaccines delivered via lipid nanoparticles (LNPs) have unique properties with effective stability, fast rate, low cost, and large-scale capability [ 25 , 26 ]. A number of mRNA vaccines that target SARS-CoV-2 RBD have been developed, which include those that target the ancestral strain and some variants, such as Omicron BA.4/5 subvariants, and their neutralizing activity and/or protective efficacy against different strains vary, depending on the SARS-CoV-2 strains or animal models tested [ 27 , 28 , 29 ]. Although SARS-CoV-2 RBD-mRNA-induced antibodies may cross-neutralize SARS-CoV infection, the neutralizing activity is relatively low [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

A Unique mRNA Vaccine Elicits Protective Efficacy against the SARS-CoV-2 Omicron Variant and SARS-CoV

Guan,

Verma,

Wang

et al. 2024

Vaccines

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The highly pathogenic coronaviruses SARS-CoV-2 and SARS-CoV have led to the COVID-19 pandemic and SARS outbreak, respectively. The receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2, particularly the Omicron variant, has frequent mutations, resulting in the reduced efficiency of current COVID-19 vaccines against new variants. Here, we designed two lipid nanoparticle-encapsulated mRNA vaccines by deleting the mutant RBD of the SARS-CoV-2 Omicron variant (SARS2-S (RBD-del)) or by replacing this mutant RBD with the conserved and potent RBD of SARS-CoV (SARS2-S (SARS-RBD)). Both mRNA vaccines were stable at various temperatures for different time periods. Unlike SARS2-S (RBD-del) mRNA, SARS2-S (SARS-RBD) mRNA elicited effective T-cell responses and potent antibodies specific to both SARS-CoV-2 S and SARS-CoV RBD proteins. It induced strong neutralizing antibodies against pseudotyped SARS-CoV-2 and SARS-CoV infections and protected immunized mice from the challenge of the SARS-CoV-2 Omicron variant and SARS-CoV by significantly reducing the viral titers in the lungs after Omicron challenge and by completely preventing SARS-CoV-induced weight loss and death. SARS2-S (SARS-RBD)-immunized serum antibodies protected naïve mice from the SARS-CoV challenge, with its protective efficacy positively correlating with the neutralizing antibody titers. These findings indicate that this mRNA vaccine has the potential for development as an effective vaccine against current and future SARS-CoV-2 variants and SARS-CoV.

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