Preclinical evaluation in hamster model of the mRNA COVID-19 vaccine candidate AfriVac 2121 (Wuhan) produced under the WHO/MPP mRNA Technology Transfer Programme.

During the COVID-19 pandemic, access to vaccines in low- and middle-income countries was limited and delayed. To address these disparities, the mRNA Technology Transfer Programme, coordinated and led by the World Health Organization and the Medicines Patent Pool, was launched. A consortium has been set up in South Africa to develop a platform for manufacturing mRNA vaccines. In this study, the preclinical evaluation of the mRNA COVID-19 vaccine candidate, AfriVac 2121 (Wuhan) manufactured in December 2022 was conducted. The hamster model was employed to assess the immunogenicity and efficacy of this COVID-19 mRNA vaccine candidate in comparison to a commercial mRNA vaccine (mRNA-1273, Moderna). Results revealed that a vaccine regimen consisting of two 5 µg doses of AfriVac 2121 (Wuhan) elicited a protective immune response against an ancestral B.1 strain of SARS-CoV-2 similar to that obtained with the mRNA-1273 vaccine. AfriVac 2121 (Wuhan) induced robust humoral immune responses against SARS-CoV-2 and protected hamsters against a SARS-CoV-2 challenge with the B.1 strain. These results have since enabled the further development of this platform for manufacturing mRNA vaccines.

COMPARING vaccine manufacturing technologies recombinant DNA vs in vitro transcribed (IVT) mRNA.

Vaccine manufacturing fosters the prevention, control, and eradication of infectious diseases. Recombinant DNA and in vitro (IVT) mRNA vaccine manufacturing technologies were enforced to combat the recent pandemic. Despite the impact of these technologies, there exists no scientific announcement that compares them. Digital Shadows are employed in this study to simulate each technology, investigating root cause deviations, technical merits, and liabilities, evaluating cost scenarios. Under this lens we provide an unbiased, advanced comparative technoeconomic study, one that determines which of these manufacturing platforms are suited for the two types of vaccines considered (monoclonal antibodies or antigens). We find recombinant DNA technology to exhibit higher Profitability Index due to lower capital and starting material requirements, pertaining to lower Minimum Selling Price per Dose values, delivering products of established quality. However, the potency of the mRNA, the streamlined and scalable synthetic processes involved and the raw material availability, facilitate faster market penetration and product flexibility, constituting these vaccines preferable whenever short product development cycles become a necessity.

Evaluating the impact of extended dosing intervals on mRNA COVID-19 vaccine effectiveness in adolescents.

BACKGROUND: Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. METHODS: We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. RESULTS: We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. CONCLUSIONS: Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Conversion of vaccines from low to high immunogenicity by antibodies with epitope complementarity.

Existing antibodies (Abs) have varied effects on humoral immunity during subsequent infections. Here, we leveraged in vivo systems that allow precise control of antigen-specific Abs and B cells to examine the impact of Ab dose, affinity, and specificity in directing B cell activation and differentiation. Abs competing with the B cell receptor (BCR) epitope showed affinity-dependent suppression. By contrast, Abs targeting a complementary epitope, not overlapping with the BCR, shifted B cell differentiation toward Ab-secreting cells. Such Abs allowed for potent germinal center (GC) responses to otherwise poorly immunogenic sites by promoting antigen capture and presentation by low-affinity B cells. These mechanisms jointly diversified the B cell repertoire by facilitating the recruitment of high- and low-affinity B cells into Ab-secreting cell, GC, and memory B cell fates. Incorporation of small amounts of monoclonal Abs into protein- or mRNA-based vaccines enhanced immunogenicity and facilitated sustained immune responses, with implications for vaccine design and our understanding of protective immunity.

LNP-mRNA vaccine prevents type 1 diabetes in non-obese diabetes mice.

Islet-antigen-specific tolerization is a key goal of experimental immunotherapies for type 1 diabetes. mRNA-based vaccines have demonstrated the feasibility of RNA delivery in inducing antigen tolerance in autoimmune diseases. In this study, mRNA vaccine, encoded tandem glutamic acid decarboxylase 65 (GAD65) epitopes and cholera toxin B subunit (CTB-GADIII), prepared by an in vitro transcription (IVT) system and encapsulated with lipid nanoparticles (LNP), was intramuscularly administered to non-obese diabetic (NOD) and cyclophosphamide (Cy)-NOD mice respectively. The results showed that the mRNA vaccines significantly reduced the incidence rate of type 1 diabetes, delayed the disease progression, improved glucose tolerance, and protected pancreatic morphology and function compared with the controls. Meanwhile, the vaccines also reduced the levels of autoantibodies to glutamic acid decarboxylase (GADA) and insulin (IAA) in the serum. Furthermore, the proportion of CD4+ T helper cell subsets was modulated in the spleen of mice treated with mRNA vaccines, in correspondence with the increased levels of IL-10 and TGF-ß in serum, suggesting the possible mechanism of immune tolerance. This study provides experimental evidence for the application of mRNA vaccines encoding self-antigens in the prevention or treatment of type 1 diabetes.

Association of COVID-19 Vaccination With Risk of Medically Attended Postacute Sequelae of COVID-19 During the Ancestral, Alpha, Delta, and Omicron Variant Eras.

Background: Uncertainty exists regarding the effectiveness of COVID-19 vaccine to prevent postacute sequelae of COVID-19 (PASC) following a breakthrough infection. While most studies based on symptom surveys found an association between preinfection vaccination status and PASC symptoms, studies of medically attended PASC are less common and have reported conflicting findings. Methods: In this retrospective cohort of patients with an initial SARS-CoV-2 infection who were continually empaneled for primary care in a large US health system, the electronic health record was queried for preinfection vaccination status, demographics, comorbidity index, and diagnosed conditions. Multivariable logistic regression was used to model the outcome of a medically attended PASC diagnosis within 6 months of SARS-CoV-2 infection. Likelihood ratio tests were used to assess the interaction between vaccination status and prevalent variant at the time of infection and between vaccination status and hospitalization for SARS-CoV-2 infection. Results: During the observation period, 6.9% of patients experienced medically attended and diagnosed PASC. A diagnosis of PASC was associated with older age, female sex, hospitalization for the initial infection, and an increased severity-weighted comorbidity index and was inversely associated with infection during the Omicron period. No difference in the development of diagnosed PASC was observed between unvaccinated patients and those vaccinated with either 2 doses of an mRNA vaccine or >2 doses. Conclusions: We found no association between vaccination status at the time of infection and development of medically diagnosed PASC. Vaccine remains an important measure to prevent SARS-CoV-2 infection and severity. Further research is needed to identify effective measures to prevent and treat PASC.

Newly developed mRNA vaccines induce immune responses in Litopenaeus vannamei shrimps during primary vaccination.

White spot syndrome virus (WSSV) causes highly destructive infection in crustacean aquaculture, often resulting in 100% mortality within a week. However, there is lack of studies addressing the safety issues of WSSV vaccines in shrimps. In this study, WSSV VP28 mRNA vaccines were developed using codon deoptimization approach. These vaccines were administered to Litopenaeus vannamei shrimps at various dosages to access their safety and the shrimps' immune responses using quantification PCR (qPCR). The findings of this study indicate that the expression level of codon deoptimized VP28 mRNA vaccines are lower compared to the wild type VP28 vaccines, as observed through a comparison of bioinformatic predictions and experimental results. Additionally, the total haemocyte count (THC) in shrimps injected with codon deoptimized VP28 vaccine was higher than those injected with wild type VP28 vaccines. Furthermore, the expression of immune-related genes differed between codon deoptimized and wild type VP28 vaccines. In summary, the results suggest that 0.01µg codon deoptimized VP28-D1 mRNA vaccine is the most promising WSSV mRNA vaccine, displaying low pathogenicity and expression in shrimps. To the best of our knowledge, this research represents the first attempt to attenuate WSSV using codon deoptimization method and development of a potential mRNA vaccine for shrimp purpose. The study addresses an important gap in shrimp vaccine research, offering potential solutions for WSSV control in shrimps.

Personalized mRNA vaccine combined with PD-1 inhibitor therapy in a patient with advanced esophageal squamous cell carcinoma.

Therapeutic cancer vaccines are valuable tools for educating the immune system to fight tumors precisely. Cancer cells are characterized with genetic instability and abundant somatic mutations, leading to the production of tumor specific antigens (TSA) called neoantigens. The main goal of neoantigen-based cancer vaccines is to activate the immune system and elicit effective tumor-specific T-cell responses. There have been no reports of advanced esophageal squamous cell carcinoma (ESCC) cases achieving partial remission after personalized mRNA (messenger RNA) vaccine treatment. As personalized neoantigen-based immunotherapies are emerging, here we report a 67-year-old male patient diagnosed with ESCC and multiple enlarged mediastinal lymph nodes, where mRNA vaccines were used for the first time. Tissue samples from the recurrence focus in the esophagus were subjected to whole transcriptome sequencing. The neoantigens were identified by bioinformatics analyses. The top 20 neoantigens were selected to compose the polyneoantigen vaccine, which were administered at 1 mg every 3 weeks for 4 cycles in combination with a PD-1 (programmed death-1) inhibitor. The patient was boosted with a single dose of the PD-1 inhibitor 8 weeks after the 4th cycle. In addition, immune responses were evaluated before and after the 4 cycles of vaccine therapy, and the lesions were evaluated by imaging examination. Our results revealed that neoantigen-based vaccines significantly activated the tumour-specific immune response. TCR (T cell receptor) V-J pairing analysis showed an increase in the abundance of oligoclonal TCRs, indicating improved homogeneity. No grade 3 or higher drug-related adverse events were observed, except for grade 4 thrombocytopenia caused by PD-1 inhibitor treatment. The patient achieved a partial response (PR), with a progression-free survival (PFS) time of 457 days, the OS (overall survival) time of 457 days, and DOR (duration of response) of 377 days. Our report suggests that combining the personalized mRNA vaccine therapy with PD-1 blockade therapy may be an effective treatment strategy for patient with advanced esophageal cancer. However, further clinical trials are necessary to confirm the efficacy and safety of personalized neoantigen-based immunotherapies in the treatment of advanced ESCC. This trial is registered with ClinicalTrials.gov, NCT03468244 on March 16, 2018, and is now complete.

Proteomics Exploration of Brucella melitensis to Design an Innovative Multi-Epitope mRNA Vaccine.

Brucellosis is a chronic and debilitating disease in humans, causing great economic losses in the livestock industry. Making an effective vaccine is one of the most important concerns for this disease. The new mRNA vaccine technology due to its accuracy and high efficiency has given promising results in various diseases. The objective of this research was to create a novel mRNA vaccine with multiple epitopes targeting Brucella melitensis. Seventeen antigenic proteins and their appropriate epitopes were selected with immunoinformatic tools and surveyed in terms of toxicity, allergenicity, and homology. Then, their presentation and identification by MHC cells and other immune cells were checked with valid tools such as molecular docking, and a multi-epitope protein was modeled, and after optimization, mRNA was analyzed in terms of structure and stability. Ultimately, the immune system's reaction to this novel vaccine was evaluated and the results disclosed that the designed mRNA construct can be an effective and promising vaccine that requires laboratory and clinical trials.

Identification of immunity- and ferroptosis-related signature genes as potential design targets for mRNA vaccines in AML patients.

Immune-associated ferroptosis plays an important role in the progression of acute myeloid leukemia (AML); however, the targets that play key roles in this process are currently unknown. This limits the development of mRNA vaccines based on immune-associated ferroptosis for clinical therapeutic applications. In this study, based on the rich data resources of the TCGA-LAML cohort, we analyzed the tumor mutational burden (TMB), gene mutation status, and associations between immune and ferroptosis genes to reveal the disease characteristics of AML patients. To gain a deeper understanding of differentially expressed genes, we applied the Limma package for differential expression analysis and integrated data sources such as ImmPort Shared Data and FerrDb V2. Moreover, we established gene modules related to TMB according to weighted gene coexpression network analysis (WGCNA) and explored the functions of these modules in AML and their relationships with TMB. We focused on the top 30 most frequent genes through a detailed survey of missense mutations and single nucleotide polymorphisms (SNPs) and selected potentially critical gene targets for subsequent analysis. Based on the expression of these genes, we successfully subgrouped AML patients and found that the subgroups associated with TMB (C1 and C2) exhibited significant differences in survival. The differences in the tumor microenvironment and immune cells between C1 and C2 patients were investigated with the ESTIMATE and MCP-counter algorithms. A predictive model of TMB-related genes (TMBRGs) was constructed, and the validity of the model was demonstrated by categorizing patients into high-risk and low-risk groups. The differences in survival between the high-risk patients and high-TMB patients were further investigated, and potential vaccine targets were identified via immune cell-level analysis. The identification of immunity- and ferroptosis-associated signature genes is an independent predictor of survival in AML patients and provides new information on immunotherapy for AML.

A decavalent composite mRNA vaccine against both influenza and COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 has had a persistent and significant impact on global public health for 4 years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.IMPORTANCEAmidst the ongoing and emerging respiratory viral threats, particularly the concurrent and sequential spread of SARS-CoV-2 and influenza, our research introduces FLUCOV-10. This novel mRNA-based combination vaccine, designed to counteract both influenza and COVID-19, by incorporating genes for surface glycoproteins from various influenza viruses and SARS-CoV-2 variants. This combination vaccine was highly effective in preclinical trials, generating strong immune responses and ensuring protection against both matching and heterologous strains of influenza viruses and SARS-CoV-2. FLUCOV-10 represents a significant step forward in our ability to address respiratory viral threats, showcasing potential as a singular, adaptable vaccine solution for global health challenges.

Antibody response to non-mRNA SARS-CoV-2 vaccine in kidney transplant recipients.

BACKGROUND: Kidney transplant recipients (KTRs) show poor antibody response to the SARS-CoV-2 vaccine. There is limited data on immune response to non-mRNA vaccines in KTRs. We studied the antibody response to the SARS-CoV-2 non-mRNA vaccine in a cohort of kidney transplant recipients. METHODS: We included KTRs following up in the tertiary care transplant outpatient clinic from February to April 2022. SARS-CoV-2 spike protein IgG antibody titers were measured using chemiluminescence immunoassay. Data on demographic, clinical, and laboratory characteristics were collected, and patients were characterized by the history of Coronavirus disease 2019 (COVID-19) infection in the past and the number of vaccine doses received. Predictors of antibody response were obtained using multivariate regression analysis. RESULTS: S1/S2 IgG anti-SARS-CoV-2 antibodies were detected in 197 (87.94%) of 224 KTRs with a median [IQR] titers of 307.5 AU/ml [91 AU/ml - 400 AU/ml]. Neutralizing range antibody titers were found in 170/224 (75.9%) KTRs. Diabetes at the time of vaccination was associated with poorer antibody response (aOR 0.31, 95% confidence interval [CI] - 0.10, 0.90; p = 0.032) and vaccination with Covishield™ (ChAdOx1 nCoV- 19 Recombinant CoronaVirus Vaccine) showed higher antibody response as compared to Covaxin™ (BBV152) (aOR 5.04, 95% CI - 1.56, 16.22; p = 0.007). Graft dysfunction at baseline was associated with poorer antibody response. CONCLUSIONS: KTRs showed good antibody response after SARS-CoV-2 vaccination with non-mRNA vaccines. Diabetes and graft dysfunction were associated with poor seroconversion rates.

Robust SARS-CoV-2-neutralizing antibodies sustained through 6 months post XBB.1.5 mRNA vaccine booster.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies are substantially expanded 1 month after a shot of XBB.1.5 monovalent mRNA vaccine (XBB.1.5 MV) booster, but the durability of this response remains unknown. Here, we address this question by performing neutralization assays on four viral variants (D614G, BA.5, XBB.1.5, and JN.1) using sera from participants obtained at ∼1 month, ∼3 months, and ∼6 months post an XBB.1.5 MV booster. Our findings indicate that the resulting neutralizing antibody titers are robust and generally remain at stable levels for the study period, similar to those following XBB infection. Importantly, this durability of neutralizing antibody titers contrasts with the decline observed after a booster of the original monovalent or BA.5 bivalent mRNA vaccine. Our results are in line with the recent national data from the Centers for Disease Control and Prevention, showing that the efficacy against symptomatic SARS-CoV-2 infection is sustained for up to 4 months after an XBB.1.5 MV booster.

Fourth dose bivalent COVID-19 vaccines outperform monovalent boosters in eliciting cross-reactive memory B cells to Omicron subvariants.

Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. Here, we characterized the RBD-specific memory B cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, in direct comparison with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one month after a fourth dose with a monovalent or a BA.1 or BA.5 bivalent vaccine. Serum neutralizing antibodies (NAb) were quantified, as well as RBD-specific Bmem with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. Both bivalent vaccines elicited higher NAb titers against Omicron subvariants compared to the monovalent vaccine. Following either vaccine type, recipients had slightly increased WH1 RBD-specific Bmem numbers. Both bivalent vaccines significantly increased WH1 RBD-specific Bmem binding of all Omicron subvariants tested by flow cytometry, while recognition of Omicron subvariants was not enhanced following monovalent vaccination. IgG1+ Bmem dominated the response, with substantial IgG4+ Bmem only detected in recipients of an mRNA vaccine for their primary dose. Thus, Omicron-based bivalent vaccines can significantly boost NAb and Bmem specific for ancestral WH1 and Omicron variants and improve recognition of descendent subvariants by pre-existing, WH1-specific Bmem beyond that of a monovalent vaccine. This provides new insights into the capacity of variant-based mRNA booster vaccines to improve immune memory against emerging SARS-CoV-2 variants and potentially protect against severe disease. ONE-SENTENCE SUMMARY: Omicron BA.1 and BA.5 bivalent COVID-19 boosters, used as a fourth dose, increase RBD-specific Bmem cross-recognition of Omicron subvariants, both those encoded by the vaccines and antigenically distinct subvariants, further than a monovalent booster.

Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs.

Nucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unlike SARS-CoV-2 neutralizing antibodies that are readily made, HIV-1 bnAb induction is disfavored by the immune system because of the rarity of bnAb B cell precursors and the cross-reactivity of bnAbs targeting certain Env epitopes with host molecules, thus requiring optimized immunogen design. The use of protein nanoparticles (NPs) has been reported to enhance B cell germinal center responses to HIV-1 Env. Here, we report our experience with the expression of Env-ferritin NPs compared with membrane-bound Env gp160 when encoded by modified mRNA. We found that well-folded Env-ferritin NPs were a minority of the protein expressed by an mRNA design and were immunogenic at 20 µg but minimally immunogenic in mice at 1 µg dose in vivo and were not expressed well in draining lymph nodes (LNs) following intramuscular immunization. In contrast, mRNA encoding gp160 was more immunogenic than mRNA encoding Env-NP at 1 µg dose and was expressed well in draining LN following intramuscular immunization. Thus, analysis of mRNA expression in vitro and immunogenicity at low doses in vivo are critical for the evaluation of mRNA designs for optimal immunogenicity of HIV-1 immunogens.IMPORTANCEAn effective HIV-1 vaccine that induces protective antibody responses remains elusive. We have used mRNA technology for designs of HIV-1 immunogens in the forms of membrane-bound full-length envelope gp160 and envelope ferritin nanoparticle. Here, we demonstrated in a mouse model that the membrane-bound form induced a better response than envelope ferritin nanoparticle because of higher in vivo protein expression. The significance of our research is in highlighting the importance of analysis of mRNA design expression and low-dose immunogenicity studies for HIV-1 immunogens before moving to vaccine clinical trials.

An mpox quadrivalent mRNA vaccine protects mice from lethal vaccinia virus challenge.

The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G4S1)3 in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 µg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 µg and 20 µg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection.

A spike-based mRNA vaccine that induces durable and broad protection against porcine deltacoronavirus in piglets.

Coronaviruses (CoVs) are important pathogens for humans and other vertebrates, causing severe respiratory and intestinal infections that have become a threat to public health because of the potential for interspecies transmission between animals and humans. Therefore, the development of safe, effective vaccines remains a top priority for the control of CoV infection. The unique immunological characteristics of vaccines featuring messenger RNA (mRNA) present an advantageous tool for coronavirus vaccine development. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines: one encoding full-length spike (S) protein and the other encoding the spike ectodomain (Se) from porcine deltacoronavirus (PDCoV). Fourteen days after primary immunization, both mRNA vaccines induced high levels of immunoglobulin G and neutralizing antibodies in mice, with the S vaccine showing better performance than the Se vaccine. Passive immune protection of the S mRNA vaccine in suckling piglets was confirmed by the induction of robust PDCoV-specific humoral and cellular immune responses. The S mRNA vaccine also showed better protective effects than the inactivated vaccine. Our results suggest that the novel PDCoV-S mRNA-LNP vaccine may have the potential to combat PDCoV infection. IMPORTANCE: As an emerging porcine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) has the potential for cross-species transmission, attracting extensive attention. Messenger RNA (mRNA) vaccines are a promising option for combating emerging and re-emerging infectious diseases, as evidenced by the demonstrated efficacy of the COVID-19 mRNA vaccine. Here, we first demonstrated that PDCoV-S mRNA-lipid nanoparticle (LNP) vaccines could induce potent humoral and cellular immune responses in mice. An evaluation of passive immune protection of S mRNA vaccines in suckling piglets confirmed that the protective effect of mRNA vaccine was better than that of inactivated vaccine. This study suggests that the PDCoV-S mRNA-LNP vaccine may serve as a potential and novel vaccine candidate for combating PDCoV infection.

The Impact of COVID-19 Vaccination Side-Effects on Work Attendance among Saudi Healthcare Workers.

OBJECTIVE: This cross-sectional-survey-based study aimed to investigate the severity of side-effects from Coronavirus disease (COVID-19) mRNA (Pfizer, Moderna), viral vector DNA (Oxford-AstraZeneca, J&J/Janssen), inactivated virus (Sinopharm, Sinovac), and other vaccines among healthcare workers (HCWs) in Saudi Arabia, focusing on their impact on work attendance. METHODS: A total of 894 HCWs residing in Saudi Arabia participated in this study from March 2023 to May 2023. Participants completed an online questionnaire assessing demographic information, vaccination status, comorbidities, vaccine side-effects, and missed work information after vaccination. Descriptive statistics and chi-square tests were used for data analysis. RESULTS: The majority of participants were female (83.7%) and aged 25-34 years (42.8%). Most participants were predominantly vaccinated with mRNA vaccines. Common side-effects included pain at the injection site, fatigue, fever, and chills. However, no significant association was found between vaccine type, side-effects, and work absenteeism. While demographic factors such as age and healthcare profession did not influence work absenteeism, variations were observed among different racial groups. CONCLUSION: COVID-19 vaccination among HCWs in Saudi Arabia is associated with common side-effects, but their impact on work attendance is not significant. Understanding these implications can inform strategies to support the healthcare workforce and mitigate the impact on patient care and staffing during the ongoing COVID-19 pandemic.

Preclinical Efficacy of Cap-Dependent and Independent mRNA Vaccines against Bovine Viral Diarrhea Virus-1.

Bovine viral diarrhea virus (BVDV) is an RNA virus associated with severe economic losses in animal production. Effective vaccination and viral surveillance are urgent for the prevention and control of BVDV infection. However, the application of traditional modified live vaccines and inactivated vaccines is faced with tremendous challenges. In the present study, we describe the preclinical efficacy of two BVDV mRNA vaccines tested in mice and guinea pigs, followed by a field trial in goats, where they were compared to a commercial vaccine (formaldehyde inactivated). The two mRNAs were engineered to express the envelope protein E2 of BVDV-1, the most prevalent subtype across the world, through a 5' cap-dependent or independent fashion. Better titers of neutralizing antibodies against BVDV-1 were achieved using the capped RNA in the sera of mice and guinea pigs, with maximum values reaching 9.4 and 13.7 (by -log2), respectively, on the 35th day post-vaccination. At the same time point, the antibody levels in goats were 9.1 and 10.2 for the capped and capless RNAs, respectively, and there were no significant differences compared to the commercial vaccine. The animals remained healthy throughout the experiment, as reflected by their normal leukogram profiles. Collectively, our findings demonstrate that mRNA vaccines have good safety and immunogenicity, and we laid a strong foundation for the further exploitation of efficient and safe BVDV vaccines.