mRNA-based vaccines are assured to significantly boost biopharmaceuticals since outbreak of coronavirus disease- 2019. Respiratory infections, such as influenza, SARS, MERS, COVID-19, and respiratory syncytial virus, often have high transmission rates due to their airborne spread. Respiratory infections can lead to severe illness and death. These outbreaks can cause substantial economic and social disruption, as seen with the COVID-19 pandemic. In our interconnected world, respiratory diseases can spread rapidly across borders. mRNA-based vaccines (e.g. mRNA-1283) can reduce the transmission by creating immunity in the population, thus lowering the incidence and spread of these diseases. Vaccines are crucial for global health security, helping to prevent local outbreaks from becoming global pandemics. Nevertheless, various concerns remain such as intracellular delivery, susceptibility to degradation by catalytic hydrolysis, and instability due to several physiological conditions. Therefore, an hour needed to address these challenges and opportunities for attaining high-quality and stable mRNA-based vaccines with novel drug delivery systems. The authors contributed an extensive review of the mRNA-based clinical development, progress in stability, and delivery challenges to mitigate market needs. In addition, the authors discuss crucial advances in the growth of mRNA-based vaccines to date; which dominate an extensive scope of therapeutic implementation. Finally, recent mRNA-based vaccines in clinical trials, adjuvant benefits, and prospects are discussed.

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Preventing SARS-CoV-2 infection is of utmost importance in allogeneic hematopoietic cell transplantation patients (allo-HCT), given their heightened susceptibility to adverse outcomes associated with SARS-CoV-2 infection. However, limited data are available regarding the immune response to COVID-19 vaccines in these subjects, particularly concerning the generation and persistence of spike-specific memory response. Here, we analyzed the spike-specific memory B cells in a cohort of allo-HCT recipients vaccinated with multiple doses of the mRNA-1273 vaccine and monitored the spike-specific antibody response from baseline up to one month after the fourth dose. After the primary vaccine series, the frequency of spike-specific B cells, detected within the pool of Ig-switched CD19+ cells, significantly increased. The booster dose further induced a significant expansion, reaching up to 0.28% of spike-specific B cells. The kinetics of this expansion were slower in the allo-HCT recipients compared to healthy controls. Spike-specific IgG and ACE2/RBD binding inhibition activity were observed in 80% of the allo-HCT recipients after the first two doses, with a significant increase after the third and fourth booster doses, including in the subjects who did not respond to the primary vaccine series. Additionally, 87% of the allo-HCT recipients exhibited positive cross-inhibition activity against the BA.1 variant. Our findings provide evidence that allo-HCT recipients need repeated doses of the mRNA-1273 vaccine to induceSARS-CoV-2 specific immune response similar to that observed in healthy individuals. This is particularly crucial for vulnerable individuals who may exhibit a limited response to the primary series of SARS-CoV-2 vaccination.

COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009).
In the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18-59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 μg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009.
All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination.
LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity.
Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349.

BACKGROUND: Hereby, we describe the first case of latent mastocytosis triggered by mRNA-based vaccine to prevent COVID-19 infection.
METHODS: In a 42-year-old Arabian man affected by slight, undiagnosed mastocytosis, the second dose of the COVID-19 vaccine made more blatant his latent disease. The postvaccination diagnostic iter is illustrated and the potential reasons causing the onset of the cutaneous mastocytosis are discussed.
CONCLUSIONS: Clinicians should keep a longer follow-up of their patients after the COVID-19 vaccination, not related to few hours, for the risk of immediate-type adverse events only.

Introduction Autoimmune diseases have been linked to COVID-19 vaccines. An increasing number of cases have reported de novo immune thrombocytopenia (ITP) following mRNA COVID-19 vaccines. This study aims to investigate the incidence of de novo ITP following the mRNA COVID-19 vaccine in comparison to other non-mRNA vaccines and COVID-19. Methods Data were collected from the TriNetX global health research network, which covers over 117 million patients. Four different patient cohorts were included: those who received the mRNA COVID-19 vaccine (between 12/15/2020 - 5/1/2023), the influenza vaccine (between 01/01/2010 - 01/01/2020), tetanus, diphtheria, and pertussis/tetanus and diphtheria (Tdap/Td) vaccines (between 01/01/2010 - 01/01/2020), and those who had COVID-19 (between 01/01/2020 - 05/01/2023). A comparative analysis was conducted to examine the occurrence of de novo ITP within three weeks after receiving mRNA COVID-19 vaccine, non-mRNA vaccines, or upon diagnosis of COVID-19. Additionally, a comparative analysis was performed after 1:1 propensity score matching to balance baseline characteristics (age, sex, and race). Results The overall event rate was 0.07 per 10,000 for the mRNA COVID-19 vaccine, 0.25 per 10,000 for the influenza vaccine, and 0.28 per 10,000 for the Tdap/Td vaccines. Additionally, the incidence of de novo ITP following COVID-19 was 0.30 per 10,000. Those who received the influenza vaccine and Tdap/Td vaccines had higher rates of de novo ITP compared to the mRNA COVID-19 vaccine group, with a relative risk of 3.48 and 3.88, respectively. The occurrence of de novo ITP following COVID-19 was significantly higher compared to that following the mRNA COVID-19 vaccine, with a relative risk of 4.27. Post-propensity score matching analysis produced similar outcomes. Conclusions The findings of this study suggest that the incidence of de novo ITP is significantly lower following mRNA-based COVID-19 vaccines compared to non-mRNA vaccines and COVID-19.

Since the beginning of the mass immunization of patients with multiple sclerosis (MS), many data on the efficacy and safety of COVID-19 vaccines have been produced. Considering that MS is an autoimmune disease and that some disease-modifying therapies (DMTs) could decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety of these vaccines in terms of AEFI occurrence and the antibody response after MS patients had received the third dose. Two hundred and ten patients (64.8% female; mean age: 46 years) received the third dose of the mRNA-based COVID-19 vaccine and were included in the study. Third doses were administered from October 2021 to January 2022. The majority of patients (n = 193) were diagnosed with RRMS and EDSS values were ≤3.0 in 72.4% of them. DMTs most commonly used by included patients were interferon Beta 1-a, dimethyl fumarate, natalizumab and fingolimod. Overall, 160 patients (68.8% female) experienced 294 AEFIs, of which about 90% were classified as short-term, while 9.2% were classified as long-term. The most commonly reported following the booster dose were pain at the injection site, flu-like symptoms, headache, fever and fatigue. Regarding the immune response, consistently with literature data, we found that patients receiving ocrelizumab and fingolimod had lower IgG titer than patients receiving other DMTs.

UNASSIGNED: Heterologous priming with the inactivated SARS-CoV-2 vaccine (CoronaVac) and boosting with mRNA-based COVID-19 vaccine (Moderna or Pfizer) is currently recommended in Indonesia. The reactogenicity data of these heterologous vaccine regimens are not entirely available, particularly in young adults. The present study, therefore, aimed to evaluate the solicited local and systemic reactions in the first seven days post-vaccination either with Moderna or Pfizer vaccine among previous recipients of two doses of CoronaVac.
UNASSIGNED: An electronic-based cross-sectional study was conducted among medical students at the Pelita Harapan University, Banten, Indonesia, who received mRNA-based COVID-19 vaccine following two doses of CoronaVac. Samples were collected using a cluster sampling technique. Comparison between groups was performed by Fisher\'s exact test.
UNASSIGNED: A total of 72 participants, 23 (32%) of which received the Moderna vaccine and 49 (68%) received the Pfizer vaccine, were included in this study. The median age of participants was 21 (IQR 19-22) years old. The most common local and systemic events for mRNA-based COVID-19 vaccines were injection site pain, fever, headache, fatigue, myalgia, and arthralgia. Solicited local and systemic reactions were reported more frequently in Moderna recipients than Pfizer recipients. Most local and systemic reactions were graded as mild to moderate and did not lead to hospitalization.
UNASSIGNED: The reactogenicity of the heterologous prime-boost with CoronaVac and mRNA-based COVID-19 vaccine booster among young adults is reassuring, and no unexpected concerns were identified.

Coronavirus disease 2019 (COVID-19) mRNA vaccine-related cases of pericarditis and myocarditis have been reported infrequently. Most of the patients usually present within a week of the vaccine, and on average, most of the cases were reported after the second dose of vaccine within two to four days. Chest pain was the most common presentation, and fever and shortness of breath were the other commonly reported symptoms. The patients can have positive cardiac markers and electrocardiogram (EKG) changes, and the cases can be mistaken for cardiac emergencies. We present a 17-year-old male patient with sudden onset substernal chest pain for two days who got the third dose of the Pfizer-BioNTech mRNA vaccine within 24 hours prior. EKG was remarkable for diffuse ST elevations, and troponins were elevated. Later, the cardiac magnetic resonance imaging confirmed the findings of myopericarditis. The patient was treated with colchicine and non-steroidal anti-inflammatory drugs (NSAIDs), completely recovered, and is doing fine to date. This case hights that post-vaccine myocarditis can be mistaken and early diagnosis and management can prevent unnecessary interventions.

The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has urged scientists to present some novel vaccine platforms during this pandemic to provide a rather prolonged immunity against this respiratory viral infection. In spite of many campaigns formed against the administration of mRNA-based vaccines, those platforms were the most novel types, which helped us meet the global demand by developing protection against COVID-19 and reducing the development of severe forms of this respiratory viral infection. Some societies are worry about the COVID-19 mRNA vaccine administration and the potential risk of genetic integration of inoculated mRNA into the human genome. Although the efficacy and long-term safety of mRNA vaccines have not yet been fully clarified, obviously their application has switched the mortality and morbidity of the COVID-19 pandemic. This study describes the structural features and technologies used in producing of COVID-19 mRNA-based vaccines as the most influential factor in controlling this pandemic and a successful pattern for planning to produce other kind of genetic vaccines against infections or cancers.