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Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines.

ABSTRACT: The design of Pfizer/BioNTech and Moderna mRNA vaccines involves many different types of optimizations. Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs. The mRNA components of the vaccine need to have a 5'-UTR to load ribosomes efficiently onto the mRNA for translation initiation, optimized codon usage for efficient translation elongation, and optimal stop codon for efficient translation termination. Both 5'-UTR and the downstream 3'-UTR should be optimized for mRNA stability. The replacement of uridine by N1-methylpseudourinine (Ψ) complicates some of these optimization processes because Ψ is more versatile in wobbling than U. Different optimizations can conflict with each other, and compromises would need to be made. I highlight the similarities and differences between Pfizer/BioNTech and Moderna mRNA vaccines and discuss the advantage and disadvantage of each to facilitate future vaccine improvement. In particular, I point out a few optimizations in the design of the two mRNA vaccines that have not been performed properly.

SUBMITTER: Xia X

PROVIDER: S-EPMC8310186 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDifferences in immunogenicity between mRNA SARS-CoV-2 vaccines have not been well characterized in patients undergoing dialysis. We compared the serologic response in patients undergoing maintenance hemodialysis after vaccination against SARS-CoV-2 with BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna).MethodsWe conducted a prospective observational cohort study at 2 academic centres in Toronto, Canada, from Feb. 2, 2021, to July 20, 2021, which included 129 and 95 patients who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines, respectively. We measured SARS-CoV-2 immunoglobulin G antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD) and nucleocapsid protein (anti-NP) at 6-7 and 12 weeks after the second dose of vaccine and compared those levels with the median convalescent serum antibody levels from 211 controls who were previously infected with SARS-CoV-2.ResultsAt 6-7 weeks after 2-dose vaccination, we found that 51 of 70 patients (73%) who received BNT162b2 and 83 of 87 (95%) who received mRNA-1273 attained convalescent levels of anti-spike antibody (p < 0.001). In those who received BNT162b2, 35 of 70 (50%) reached the convalescent level for anti-RBD compared with 69 of 87 (79%) who received mRNA-1273 (p < 0.001). At 12 weeks after the second dose, anti-spike and anti-RBD levels were significantly lower in patients who received BNT162b2 than in those who received mRNA-1273. For anti-spike, 70 of 122 patients (57.4%) who received BNT162b2 maintained the convalescent level versus 68 of 71 (96%) of those who received mRNA-1273 (p < 0.001). For anti-RBD, 47 of 122 patients (38.5%) who received BNT162b2 maintained the anti-RBD convalescent level versus 45 of 71 (63%) of those who received mRNA-1273 (p = 0.002).InterpretationIn patients undergoing hemodialysis, mRNA-1273 elicited a stronger humoral response than BNT162b2. Given the rapid decline in immunogenicity at 12 weeks in patients who received BNT162b2, a third dose is recommended in patients undergoing dialysis as a primary series, similar to recommendations for other vulnerable populations.

Project description:BackgroundmRNA COVID-19 vaccines manufactured by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) have been shown to be efficacious but have not been compared in head-to-head clinical trials.MethodsWe designed this observational study to emulate a target trial of COVID-19 vaccination by BNT162b2 versus mRNA-1273 among persons who underwent vaccination in the national U.S. Veterans Affairs (VA) healthcare system from 11/12/2020 to 25/03/2021 using combined VA and Medicare electronic health records. We identified the best matching mRNA-1273 recipient(s) for each BNT162b2 recipient, using exact/coarsened-exact matching (calendar week, VA integrated service network, age buckets and Charlson comorbidity index buckets) followed by propensity score matching. Vaccine recipients were followed from the date of first vaccine dose until 25/08/2021 for the development of SARS-CoV-2 infection, SARS-CoV-2-related hospitalization or SARS-CoV-2-related death.FindingsEach group included 902,235 well-matched vaccine recipients, followed for a mean of 192 days, during which 16,890 SARS-CoV-2 infections, 3591 SARS-CoV-2-related hospitalizations and 381 SARS-CoV-2-related deaths were documented. Compared to BNT162b2, mRNA-1273 recipients had significantly lower risk of SARS-CoV-2 infection (adjusted hazard ratio [aHR] 0.736, 95% CI 0.696-0.779) and SARS-CoV-2-related hospitalization (aHR 0.633, 95% CI 0.562-0.713), which persisted across all age groups, comorbidity burden categories and black/white race. The differences between mRNA-1273 and BNT162b2 in risk of infection or hospitalization were progressively greater when the follow-up period was longer, i.e. extending to March 31, June 30 or August 25, 2021. These differences were more pronounced when we analyzed separately the outcomes that occurred during the follow-up period from July 1 to August 25, 2021 when the Delta variant became predominant in the U.S. (aHR for infection 0.584, 95% CI 0.533-0.639 and aHR for hospitalization 0.387, 95% 0.311-0.482). SARS-CoV-2-related deaths were less common in mRNA-1273 versus BNT162b2 recipients (168 versus 213) but this difference was not statistically significant (aHR 0.808, 95% CI 0.592-1.103).InterpretationIn conclusion, although absolute rates of infection, hospitalization and death in both vaccine groups were low regardless of the vaccine received, our data suggests that compared to BNT162b2, vaccination with mRNA-1273 resulted in significantly lower rates of SARS-CoV-2-infection and SARS-CoV-2-related hospitalization. These differences were greater with longer follow-up time since vaccination and even more pronounced in the Delta variant era.FundingU.S. Department of Veterans Affairs, grant numbers COVID19-8900-11 and C19 21-278.

Project description:Introduction and importanceMessenger RNA vaccines, commonly known as mRNA vaccines, are the first COVID-19 vaccines that have been authorized and licensed in the United States. Two mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) are available. Mass vaccination remains the most critical way to halt the spread of the COVID pandemic. The most common adverse effects of the COVID vaccines are headache, muscular soreness, weariness, redness, swelling, and tenderness at the injection site. The dermatological adverse effects of mRNA vaccines, on the other hand, are little understood. We present a case of bullous fixed medication eruption following delivery of the second dose of Pfizer's Covid-19 vaccination.Case presentationWe discuss the case of a 78-year-old man who went to the Emergency Department at King Fahad Medical City in Riyadh, Saudi Arabia, with numerous bullae throughout his extremities one day after receiving the second dosage of Pfizer Covid-19 vaccine. The bullae began three days before his presentation, and they were preceded by intense pruritus and urticated plaques. A skin biopsy was performed which revealed IgG (+1), IgM (+1), and C3 (+1) staining of the basement membrane. Another punch skin biopsy taken from an intact bulla was suboptimal compressing of dermal tissue only, revealing modest perivascular lymphocytic infiltrative and scattered eosinophils. This pathological picture with superficial perivascular inflammatory dermatitis, and the presence of eosinophils suggests drug-induced bullous pemphigoid. The patient was treated with topical and systemic corticosteroids, fusidic acid cream, and emollients after a confirmed diagnosis of bullous pemphigoid was obtained. He was hospitalized for 3 weeks as a case of severe sepsis due to a skin infection, and he was started initially on empiric antibiotics with piperacillin-tazobactam plus vancomycin that was later upgraded to meropenem and vancomycin based on the results of the blood and wound cultures. The patient suffered a pulmonary embolism on the second day of hospitalization and was placed on a heparin infusion that could potentially contribute to his death one month after discharge from our hospital.Clinical discussionBullous pemphigoid is the most frequent autoimmune bullous disease. It occurs in the elderly. The cause of this disease is unknown, although it sometimes can be triggered by taking certain medications. Two case reports have also revealed bullous pemphigoid eruption following immunization. One case report reported a 78-year-old lady with diabetes and Alzheimer's disease who developed tense bullae on her face and torso after getting the second dosage of the Pfizer-BioNTech COVID-19 Vaccine. Another case study described a 77-year-old male patient who developed generalized pruritis and bullae on erythematous bases one day after receiving the AstraZeneca COVID-19 vaccination. This new-onset bullous pemphigoid phenomenon has also been observed with other vaccinations such as rabies and swine flu.ConclusionAlthough uncommon, several dermatological side reactions like bullous eruptions have been reported following the mRNA Pfizer Covid-19 vaccination. According to this case report, Bullous pemphigoid might be caused by the mRNA- (Pfizer) Covid-19 Vaccine.

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Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines.

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