Human alphaherpesvirus 2 (HSV-2) is the main pathogen resulting human genital herpes, which poses a major threat to the socio-economic development, while there is no effective vaccine. In this study, we developed a novel lipopolyplex (LPP)-delivered mRNA vaccine expressing the HSV-2 envelope glycoprotein gD and evaluated its immunogenicity in mice. The mRNA vaccine was prepared from the genetically modified gD mRNA synthesized in vitro combined with the LPP delivery platform and it was named gD-ORI mRNA. The expression of gD antigen in the mRNA vaccine was validated in vitro by Western blotting and indirect immunofluorescence assay, then the immune responses induced by this mRNA vaccine in mice were evaluated. The immunization with gD mRNA alone induced strong humoral and cellular immune responses in mice. Robust and long-lasting gD-specific IgG antibodies were detected in the mouse serum after booster immunization with gD-ORI mRNA. The immunized mice exhibited a Th1/Th2 balanced IgG response and robust neutralizing antibodies against HSV-2, and a clear dose-response relationship was observed. The gD-specific IgG antibodies were maintained in mice for a long time, up to 18 weeks post-booster immunization. At the same time, multifunctional gD-specific CD4⁺ and CD8⁺ T cells in vaccinated mice were detected by intracellular cytokine staining (ICS). This novel gD-expressing mRNA vaccine delivered by LPP induces strong and long-lasting immune responses in mice post booster immunization and has a promising prospect for development and application. This study provides scientific evidence and reference for the development of a new mRNA vaccine for HSV-2.
Animals ; Herpesvirus 2, Human/genetics* ; Viral Envelope Proteins/genetics* ; Mice ; Herpes Genitalis/immunology* ; RNA, Messenger/immunology* ; Female ; Mice, Inbred BALB C ; Antibodies, Viral/blood* ; mRNA Vaccines/immunology* ; Antibodies, Neutralizing/blood* ; Humans

Objectives: The World Health Organization recently revised their recommendations and considered healthy children and adolescents as low priority group for COVID-19 vaccine. This review comprehensively assessed existing clinical evidence on COVID-19 vaccine in 12-17 years old. Methods: Included in this review were any type of study that investigated the efficacy, immunogenicity, safety, and effectiveness of COVID-19 vaccine on protection against SARS-COV-2 infection in 12-17 years old. Various electronic databases were searched up to March 15, 2023. Studies were screened, data extracted, risk of bias appraised, and certainty of evidence was judged using GRADE. Review Manager 5.4 was used to estimate pooled effects. Difference between the two groups was described as mean difference for continuous variables and as relative risk or odds ratio for categorical variables. Results: There were six randomized controlled trials and 16 effectiveness studies (8 cohorts and 8 case control). Low certainty evidence showed that BNT162b2 (Pfizer) was effective, immunogenic, and safe in healthy adolescents. There were 15 effectiveness studies on BNT162b2 (Pfizer) in healthy adolescent and one on immunocompromised patients. It was protective against infection with any of the variants, with higher protection against Delta than Omicron. BNT162b2 is protective against hospitalization and emergency and urgent care (high certainty); and critical care and MIS-C (low). Very low certainty evidence noted that BNT 162b2 was also immunogenic in 12-21 years old with rheumatic diseases while on immunomodulatory treatment but with possible increased exacerbation of illness. Low certainty evidence demonstrated that mRNA-1273 (Moderna) was effective, immunogenic, and safe. Low to very low certainty evidence were noted on the safety and immunogenicity of two vector base vaccines (ChAdOx1-19 and Ad5 vector COVID vaccine) and two inactivated vaccines (CoronaVac and BBIBP CorV). Conclusion There is presently low certainty evidence on the use of RNA vaccines in 12-17 years old. The recommendation on its use is weak. There is presently insufficient evidence for the use of inactivated and vector-based COVID-19 vaccines. Different countries should consider whether to vaccinate healthy adolescent without comprising the other recommended immunization and health priorities that are crucial for this age group. Other factors including cost-effectiveness of vaccination and disease burden should be accounted.
mRNA Vaccines ; Vaccines, Inactivated

INTRODUCTION: Localised swelling at sites of filler injections has been reported in the Moderna mRNA-1273 coronavirus disease 2019 (COVID-19) vaccine trial. METHODS: We conducted a review of the existing data and literature on the potential pathophysiology for this adverse event and its potential management. RESULTS: Data from the Moderna and Pfizer COVID-19 vaccine Phase 3 trial and one case series were available. Three out of 30,400 subjects developed possible filler reaction in the Moderna trial. Two other cases were reported after emergency use authorisation. Reactions occurred at a mean of 1.4 days post-vaccination. Fillers were injected at a mean of 14.1 months before vaccination. Areas involved included lips, infraorbital areas and tear troughs. Treatment included observation, corticosteroids, antihistamine, hyaluronidase and 5-fluorouracil. CONCLUSION Rare, self-limiting adverse reactions to dermal fillers have been reported following COVID-19 vaccination. Clinicians should be aware of this clinical phenomenon and its management, as vaccination is carried out globally.
Humans ; 2019-nCoV Vaccine mRNA-1273/adverse effects* ; Cosmetic Techniques/adverse effects* ; COVID-19/prevention & control* ; COVID-19 Vaccines/administration & dosage* ; Dermal Fillers/administration & dosage* ; Edema/chemically induced* ; Injection Site Reaction/etiology*

Cancer remains a major global health challenge, with conventional treatments like chemotherapy and radiotherapy often hindered by significant side effects, lack of specificity, and limited efficacy in advanced cases. Among emerging therapeutic strategies, mRNA vaccines have shown remarkable potential due to their adaptability, rapid production, and capability for personalized cancer treatment. This review provides an in-depth analysis of messenger RNA (mRNA) vaccines as a therapeutic approach for cancer immunotherapy, focusing on their molecular biology, classification, mechanisms, and clinical studies. Derived from reported literature and data on clinicaltrials.gov, it examines studies on mRNA vaccines encoding tumor-specific antigens (TSAs), tumor-associated antigens (TAAs), immunomodulators, and chimeric antigen receptors (CARs) across various cancer types. The review highlights the ability of mRNA vaccines to encode TSAs and TAAs, enabling personalized cancer treatments, and classifies these vaccines into non-replicating and self-amplifying types. It further explores their mechanisms of action, including antigen presentation and immune activation, while emphasizing findings from clinical studies that demonstrate the potential of mRNA vaccines in cancer therapy. Despite their promise, challenges remain in enhancing delivery systems, improving immunogenicity, and addressing tumor heterogeneity. Overcoming these obstacles will require further investigation to fully harness the potential of mRNA vaccines in personalized cancer treatment.
Humans ; Cancer Vaccines/immunology* ; Neoplasms/immunology* ; mRNA Vaccines/therapeutic use* ; Immunotherapy/methods* ; Antigens, Neoplasm/genetics* ; RNA, Messenger/therapeutic use*

Compared with conventional vaccines, mRNA vaccines have considerable advantages in design, production, and application, especially in dealing with emerging infectious diseases. Particularly, mRNA vaccines were the first to be recommended by the World Health Organization for emergency use during the COVID-19 pandemic. A key to the design of mRNA vaccines is to ensure the stable and sufficient expression of the encoded protein in the recipient. In recent years, advances have been attained in the experimental and computational research in this area. This review focused on the progress and problems in improving the translation efficiency of mRNA vaccines in recent years, aiming to promote related research.
mRNA Vaccines ; Humans ; Protein Biosynthesis ; Vaccines, Synthetic/immunology* ; COVID-19 Vaccines/immunology* ; COVID-19/prevention & control* ; SARS-CoV-2/genetics* ; RNA, Messenger/genetics*

Background: In response to the pandemic brought about by COVID-19, vaccines were developed immediately. Together with adhering to safety protocols, vaccines are needed to help decrease the mortality and morbidity. As with any other, COVID-19 vaccines are evaluated based on efficacy and safety. Real world data is important in the recommendation of vaccines. Objectives: This study aims to assess the short-term safety of BNT162b2 COVID-19 vaccines administered to Filipino adolescents from October 15, 2021 to December 15, 2021 at the Philippine General Hospital. The number and type of local and systemic reaction within 7 days of vaccination were determined. Methods: This is a retrospective cohort study. The review of the recorded events was done through an electronic diary that was accessed from the official Electronic Medical Records of University of the Philippines-Philippine General Hospital (UP-PGH). This included solicited and prespecified local and systemic reactions that occurred within 7 days of receipt of vaccine dose. Descriptive statistics was used to present the data. Results: Out of the 1,756 BNT162b2 vaccines administered (Dose 1- 890; Dose 2- 866), 13% (N=221) indicated having adverse reaction. Injection site pain was the overall most common reaction with majority (81%) experiencing it within 7 days of vaccination. Systemic reactions made up 60% of the reactions after Dose 1 and 85% of the reactions after Dose 2. This includes tiredness, headache and fever. None of the reactions required hospitalization or further workup. Conclusion BNT162b2 vaccine has a good safety profile among adolescents vaccinated at UP-PGH, since most of the reported adverse events within 7 days of vaccination were local and systemic reactogenic reactions that did not necessitate hospitalization or work-up. No serious adverse events were reported. Further follow-up is suggested to assess longer term safety.
COVID-19 Vaccines ; mRNA Vaccines

A large number of studies have demonstrated that mRNA vaccine has been characterized as a technique with good safety, strong immunogenicity and high developmental potential, which makes it have broad prospects in immunotherapy. In recent years, the stability and in vivo delivery efficiency of mRNA vaccines have been largely addressed by the progresses in mRNA engineering and delivery innovation. And some mRNA vaccines are now clinical approved or in preclinical trials. Here, we summarize current knowledge on the research advances, technology, and application in major infectious diseases in humans and animals of mRNA vaccines, with the aim to provide a reference for improving the development of novel mRNA vaccines.
Animals ; Humans ; Communicable Diseases ; Vaccines, Synthetic/genetics* ; mRNA Vaccines

Messenger RNA (mRNA) vaccines emerge as promising vaccines to prevent infectious diseases. Compared with traditional vaccines, mRNA vaccines present numerous advantages, such as high potency, safe administration, rapid production potentials, and cost-effective manufacturing. In 2020, two COVID-19 vaccines (BNT162b2 and mRNA-1273) were approved by the Food and Drug Administration (FDA). The two vaccines showed high efficiency in combating COVID-19, which indicates the great advantages of mRNA technology in developing vaccines against emergent infectious diseases. Here, we summarize the type, immune mechanisms, modification methods of mRNA vaccines, and their applications in preventing infectious diseases. Current challenges and future perspectives in developing mRNA vaccines are also discussed.
United States ; Humans ; mRNA Vaccines ; BNT162 Vaccine ; COVID-19 Vaccines/genetics* ; Communicable Diseases ; RNA, Messenger/genetics*

BACKGROUND: Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. METHODS: Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. RESULTS: In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons. CONCLUSIONS: Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.
Adult ; Humans ; BNT162 Vaccine ; 2019-nCoV Vaccine mRNA-1273 ; Network Meta-Analysis ; Immunization Schedule ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Viral Vaccines ; mRNA Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral

Vaccines are vital tools in public health as they play critical roles in preventing and controlling infectious diseases. Vaccine technology has advanced from virus-infected lesions to live attenuated, inactivated or killed pathogens, toxoids, and subunits that consist of only specific pathogen parts needed to elicit an immune response. The progression of virus-like particle vaccines, recombinant viral-vectored vaccines, toxoids, protein or polysaccharide-based vaccines designed to conjugate with a distinct carrier protein to enhance immune reaction is a significant milestone. However, some infectious pathogens can avoid the adaptive immune system, while traditional methods may be unsuitable against non-infectious diseases like cancer. Recent studies have demonstrated the potential of messenger RNA (mRNA) vaccines as an alternative to traditional vaccine approaches. mRNA vaccines contain mRNA that encodes the specific antigen and triggers a directed immune response. The two main forms of mRNA used in the study of mRNA vaccines are conventional non-amplifying mRNA and self-amplifying mRNA (saRNA). This article discusses the mRNA vaccine structure, delivery strategies, and protective functions, focusing on mRNA vaccines’ safety and therapeutic potential. Pre-clinical research has demonstrated the broad utility of mRNA vaccines in animal models. Human clinical trials, however, are still under validation. Hence, further studies will need to focus on adapting reliable results of preclinical trials to human applications. The evidence to date suggests that mRNA vaccines are promising next-generation vaccines and, in the future, clinical trials would transform basic research into mRNA therapeutics in medical practices.
COVID-19 ; mRNA Vaccines ; Safety ; Vaccination