Safety and Efficacy of the Modified Vaccinia Ankara-Bavaria Nordic Vaccine Against Mpox in the Real World: Systematic Review and Meta-Analysis.

In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated orthopoxvirus vaccine that has been authorized by the U.S. Food and Drug Administration as the vaccine of choice for the prevention of mpox. In this study, we conducted a meta-analysis of all currently published literature on the efficacy and safety of the MVA-BN vaccine in the real world, showing that the MVA-BN vaccine is effective and safe, with efficacy of up to 75% with a single dose and up to 80% with a two-dose vaccine. Meanwhile, we found that subcutaneous injection has lower local and systemic adverse events than intradermal injection, regardless of single- or two-dose vaccination, and subcutaneous injection is better tolerated in children, the elderly, or people with underlying medical conditions. These results have important reference value for clinical practice.

Investigation of the safety and protective efficacy of an attenuated and marker M. bovis-BoHV-1 combined vaccine in bovines.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.

Phase 3 immunogenicity and safety study of a tick-borne encephalitis vaccine in healthy Japanese participants 1 year of age and older.

BACKGROUND: Tick-borne encephalitis (TBE) virus infects the central nervous system and may lead to severe neurological complications or death. This study assessed immunogenicity, safety, and tolerability of TBE vaccine in Japanese participants 1 year of age and older. METHODS: This phase 3, multicenter, single-arm, open-label study was conducted in Japanese adult (≥ 16 years) and pediatric (1-< 16 years) populations. Participants received a single 0.5-mL (adult) or 0.25-mL (pediatric) dose of TBE vaccine at each of 3 visits. The primary endpoint was the proportion of participants who were seropositive (neutralization test [NT] titer ≥ 1:10) 4 weeks after Dose 3. Secondary and exploratory endpoints included NT seropositivity rates 4 weeks after Dose 2, immunoglobulin G (IgG) seropositivity 4 weeks after Doses 2 and 3, NT geometric mean titers (GMTs), IgG geometric mean concentrations (GMCs), and geometric mean fold rises. Primary safety endpoints were frequencies of local reactions, systemic events, adverse events (AEs), and serious AEs. RESULTS: Among 100 adult and 65 pediatric participants, 99.0 % and 100.0 % completed the study, respectively. NT seropositivity was achieved in 98.0 % adult and 100.0 % pediatric participants after Dose 3; seropositivity after Dose 2 was 93.0 % and 92.3 %, respectively. In both age groups, IgG seropositivity was ≥ 90.0 % and ≥ 96.0 % after Doses 2 and 3, respectively; GMTs and GMCs were highest 4 weeks after Dose 3. Reactogenicity events were generally mild to moderate in severity and short-lived. AEs were reported by 15.0 % (adult) and 43.1 % (pediatric) of participants. No life-threatening AEs, AEs leading to discontinuation, immediate AEs, related AEs, or deaths were reported. No serious AEs were considered related to TBE vaccine. CONCLUSIONS: TBE vaccine elicited robust immune responses in Japanese participants 1 year of age and older. The 3-dose regimen was safe and well tolerated, and findings were consistent with the known safety profile of this TBE vaccine. CLINICALTRIALS: gov: NCT04648241.

Post-vaccinal distemper-like disease in two dog litters with confirmed infection of vaccine virus strain.

Modified live canine distemper virus (CDV) vaccines are widely used and considered both safe and effective. Although there are occasional literature reports of suspected vaccine-induced disease, there are none where the vaccine strain has been identified in affected tissues. Here we describe two such cases in different litters. In litter A, five of ten puppies presented with fever, anorexia, vomiting, and diarrhea a few days post-vaccination. Four puppies died or were euthanized, and autopsy revealed atypical necrosis of the lymphoid tissue. In litter B, two of five puppies developed typical neurological signs some months post-vaccination and autopsy revealed encephalitis. In all cases, affected organs tested positive for CDV on immunohistochemistry, and CDV RNA extracted from the lesions confirmed the presence of vaccine strain. Since multiple puppies from each litter were affected, it cannot be excluded without further studies that some undiagnosed inherited immunodeficiency disorder may have been involved.

Progressive shingles in a toddler due to reactivation of Varicella Zoster vaccine virus four days after infection with SARS-CoV-2; a case report.

BACKGROUND: Herpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV. CASE: Here we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash. CONCLUSION: In this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process.

Co-administration of chicken IL-2 alleviates clinical signs and replication of the ILTV chicken embryo origin vaccine by pre-activating natural killer cells and cytotoxic T lymphocytes.

IMPORTANCE: Chickens immunized with the infectious laryngotracheitis chicken embryo origin (CEO) vaccine (Medivac, PT Medion Farma Jaya) experience adverse reactions, hindering its safety and effective use in poultry flocks. To improve the effect of the vaccine, we sought to find a strategy to alleviate the respiratory reactions associated with the vaccine. Here, we confirmed that co-administering the CEO vaccine with chIL-2 by oral delivery led to significant alleviation of the vaccine reactions in chickens after immunization. Furthermore, we found that the co-administration of chIL-2 with the CEO vaccine reduced the clinical signs of the CEO vaccine while enhancing natural killer cells and cytotoxic T lymphocyte response to decrease viral loads in their tissues, particularly in the trachea and conjunctiva. Importantly, we demonstrated that the chIL-2 treatment can ameliorate the replication of the CEO vaccine without compromising its effectiveness. This study provides new insights into further applications of chIL-2 and a promising strategy for alleviating the adverse reaction of vaccines.

[Enlightening from optimizing post-authorization safety monitoring system of SARS-CoV-2 vaccines in major economies worldwide].

Ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the unprecedented rapid development and large-scale rolling out of different platform-based COVID-19 vaccines worldwide. How to effectively respond to the expected scale increasing adverse events after vaccination campaign of COVID-19 vaccines is a common problem faced by the world. A lot of countries and regions around the world have arranged in advance at different levels, optimizing the original vaccine safety monitoring system from the perspectives of strengthening the foundation and capabilities, promoting internal and external cooperation, upgrading methods, as well as improving transparency and public communication, which has ensured the good and efficient operation of the system and can provide reference for the construction of relevant fields in China.

Live IBD vaccine exacerbates disease and pathological effects of Asian lineage H9N2 LPAIV in chickens.

Avian influenza H9N2 is one of the most commonly circulating viruses in numerous Egyptian poultry farms. The Asian lineage H9N2 exhibits an immunosuppressive effect, and its pathogenicity is amplified when it co-infects with other pathogens, especially with the immunosuppressive infectious bursal disease virus (IBDV), resulting in increased mortality rates. Both vaccines and field infection can exacerbate the pathogenicity of H9N2, particularly in the bursa of Fabricius, causing more significant lymphoid depletion. To comprehend the impact of the IBD vaccine on the viral and pathogenic effect of H9N2 infection in specific pathogen-free chicks (SPF), the experiment was designed as four groups; group 1 served as the negative control, group 2 received (228E) IBD vaccine, group 3 was challenged with H9N2, and group-4 was vaccinated by the IBD vaccine then challenged with H9N2. The clinical signs, relative immune organs weights and histopathological lesion scores were recorded. The tracheal and cloacal H9N2 viral shedding were also measured. Group 4 exhibited a significant decrease (P ≤ 0.05) in the relative bursal weight and an increase in the bursal lesion score when compared with groups 1 and 3 at 4 and 8 days post-challenge (dpc). The tracheal lesion score of group-4 recorded a significant increase when compared with groups 1 and 3. The renal lesion score of group 4 achieved a significant increase when compared with 1 and 3 at 8 dpc. Also, group 4 recorded a significant increase in H9N2 shedding in comparison with groups 1 and 3. Consequently, our study concluded that routine vaccination with the IBD intermediate plus vaccine exacerbates the silent infection of H9N2 resulting in outbreaks.

Pivoting to protein: the immunogenicity and safety of protein-based NVX-CoV2373 as a heterologous booster for inactivated and viral vector COVID-19 vaccines.

INTRODUCTION: Approximately half of the 13.4 billion COVID-19 vaccine doses administered globally were inactivated or viral vector platforms. The harmonization and optimization of vaccine regimens has become a key focus of policymakers and health-care providers and presents an opportunity to reassess the continued use of pandemic-era vaccines. AREAS COVERED: Immunological evidence from studies of various homologous and heterologous regimens has been rapidly published; however, interpretation of these data is complicated by the many vaccine types and highly variable participant viral exposure and vaccination histories. Recent studies demonstrate that after primary series doses of inactivated (i.e. BBV152, and BBIBP-CorV), and viral vector (ChAdOx1 nCov-2019) vaccines, a heterologous boost with protein-based NVX-CoV2373 elicits more potent ancestral strain and omicron-specific antibody responses compared to homologous and heterologous inactivated and viral vector boosts. EXPERT OPINION: While mRNA vaccines likely yield similar performance to protein-based heterologous booster doses, the latter offers notable advantages to countries with high uptake of inactivated and viral vector vaccines in terms of transportation and storage logistics and can potentially appeal to vaccine hesitant individuals. Moving forward, vaccine-mediated protection in inactivated and viral vector recipients may be optimized with the use of a heterologous protein-based booster such as NVX-CoV2373. PIVOTING TO PROTEIN: The Immunogenicity and Safety of Protein-based NVX-CoV2373 as a Heterologous Booster for Inactivated and Viral Vector COVID-19 Vaccines. Inactivated or viral vector primary series following a booster dose with homologous or heterologous inactivated vaccines (i.e., BBV152, BBIBP-CorV), and homologous or heterologous viral vector vaccines (i.e., ChAd-Ox1 nCov-19) induces suboptimal immunogenicity compared to the enhanced immunogenicity of heterologous protein-based vaccine NVX-CoV2373.

SEROLOGIC RESPONSE AND ADVERSE EFFECTS OF RECOMBINANT CANINE DISTEMPER VACCINATION IN THREE AQUARIUM-HOUSED WALRUSES (ODOBENUS ROSMARUS).

Fatalities have been associated with phocine and canine distemper viruses in marine mammals, including pinnipeds. No data are available regarding distemper disease or vaccination in walruses. This study evaluates seroconversion and clinical adverse effects following administration of a canarypox-vectored recombinant distemper vaccination (two 1-ml doses, 3 wk apart) in three adult aquarium-housed walruses. Serum antibodies to distemper were measured using seroneutralization on blood samples collected under operant conditioning prior to and for 12 mon after vaccination or until titers were <32. All walruses seroconverted. Medium positive titers (64-128) were detected for 4 to 9.5 mon in two of three individuals. Interindividual variability was noted, with one individual displaying only low positive titers. Major swelling at the site of injection and lameness for a week following injection occurred in all three walruses. Further studies on dosing amount and interval are needed to make vaccine recommendations in this species.

POSTVACCINAL VIRAL DISEASE PRESENTATION IN TWO LITTERS OF CHEETAHS (ACINONYX JUBATUS).

Protective antibody titers against core vaccines have not been standardized for cheetahs (Acinonyx jubatus) under human care. Vaccine-induced disease has been suspected after administration of modified live virus vaccine (MLVV), but it has not been confirmed as the causative agent. MLVV and killed virus vaccines (KVV) elicit humoral response in cheetahs; however, the use of both vaccines for initial immunization in cheetah cubs <6 months old within the same population has not been reported. The current case series describes viral disease presentation in two cheetah litters after using both vaccines and presents results for serum neutralization titers against feline calicivirus (FCV) and feline herpesvirus-1 (FHV-1) and hemagglutination inhibition titers against feline panleukopenia virus (FPV). For Litter 1, MLVV was administered at 6 and 9 wk old. On week 11, one male developed ocular, oral, and dermal lesions. Viral isolation recovered FCV. Because of suspected vaccine-induced FCV, KVV was administered on weeks 13 and 16. Litter 2 was vaccinated with KVV via the same vaccination schedule. Fifty-three days after the last booster, two cubs presented with ocular, respiratory, and oral clinical signs; both were PCR positive for FHV-1. Serology reported a better anamnestic response and protective titers against FCV and FPV with the protocol used with Litter 1. In Litter 2, FCV and FHV-1 titer measurement failed in three of four cubs, limiting comparison of titers between litters. In spite of limited measurements, absence of a statistical evaluation, and presence of infection, serology showed a better humoral response when MLVV was used.

Cohort event monitoring for safety signal detection in adult individuals 18 years and above after immunisation with coronavirus disease 2019 vaccines in Nigeria.

Introduction: In Nigeria, immunisation with coronavirus disease 2019 (COVID-19) vaccines commenced in March 2021. COVISHIELD from AstraZeneca (AZ), a viral vector vaccine, was the brand administered in the first phase of vaccinations for pre-determined eligible adults 18 years and above. As more brands of COVID-19 vaccines have been introduced in Nigeria, identifying effective and safe vaccine brands is essential to pharmacovigilance and public health. The current study assessed the safety of the AZ-AZD1222 (ChAdOx1) COVID-19 vaccine in adults during the first phase of the vaccination exercise in Nigeria. Methodology: We conducted a descriptive analysis of safety data from selected vaccination sites across six states in Nigeria between June 2021 and September 2021. Respondents were monitored over 3 months for local and systemic reactions, as well as hospitalisation and mortality. Measures obtained from respondents include age, sex, pre-existing comorbidity, local and systemic reactions to vaccines, timing onset of reactions, hospitalisation and mortality. Bivariate and multivariable regression models were used to assess factors associated with vaccine reactogenicity. Results: A total of 1284 individuals were enrolled in the cohort study from the six selected states (Anambra, Borno, Edo, Katsina, Lagos and Plateau) representing the geopolitical zones of Nigeria. A total of 675 individuals or 52.6% of enrolees reported non-serious adverse effects, and only one individual or 0.08% reported a serious adverse event following immunisation in the first 7 days after vaccination. None of the enrolled participants reported adverse events requiring hospitalisation. The most common self-reported symptoms amongst vaccine recipients were tenderness at the injection site 20.9% and fever 20.3%. A majority of symptoms (55.5%) occurred on or before the 3rd day after vaccination. Multivariable logistic regression model showed that age 60 years or above (vs. 18-24 years) was significantly associated with a lower likelihood of a vaccine-related symptomatic reaction (adjusted odds ratio: 0.35; 95% confidence interval: 0.20-0.61). There was no reported mortality amongst all the enrolled and followed-up vaccine recipients. Conclusion: Our findings suggest that the safety profile of the AZ vaccine is acceptable, and the observed symptoms were mild and mostly within the first 3 days following vaccination. Vaccine recipients will benefit from counselling about potential transient reactions, and improving public awareness can potentially encourage the uptake of vaccines and reduce the spread of the COVID-19 pandemic.

First-in-human use of a modular capsid virus-like vaccine platform: an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2.

BACKGROUND: Capsid virus-like particles (cVLP) have proven safe and immunogenic and can be a versatile platform to counter pandemics. We aimed to clinically test a modular cVLP COVID-19 vaccine in individuals who were naive to SARS-CoV-2. METHODS: In this phase 1, single-centre, dose-escalation, adjuvant-selection, open-label clinical trial, we recruited participants at the Radboud University Medical Center in Nijmegen, Netherlands, and sequentially assigned them to seven groups. Eligible participants were healthy, aged 18-55 years, and tested negative for SARS-CoV-2 and anti-SARS-CoV-2 antibodies. Participants were vaccinated intramuscularly on days 0 and 28 with 6 µg, 12 µg, 25 µg, 50 µg, or 70 µg of the cVLP-based COVID-19 vaccine (ABNCoV2). A subgroup received MF59-adjuvanted ABNCoV2. Follow-up was for 24 weeks after second vaccination. The primary objectives were to assess the safety and tolerability of ABNCoV2 and to identify a dose that optimises the tolerability-immunogenicity ratio 14 days after the first vaccination. The primary safety endpoint was the number of related grade 3 adverse events and serious adverse events in the intention-to-treat population. The primary immunogenicity endpoint was the concentration of ABNCoV2-specific antibodies. The trial is registered with ClinicalTrials.gov, NCT04839146. FINDINGS: 45 participants (six to nine per group) were enrolled between March 15 and July 15, 2021. Participants had a total of 249 at least possibly related solicited adverse events (185 grade 1, 63 grade 2, and one grade 3) within a week after vaccination. Two serious adverse events occurred; one was classified as a possible adverse reaction. Antibody titres were dose-dependent with levels plateauing at a vaccination dose of 25-70 µg ABNCoV2. After second vaccination, live virus neutralisation activity against major SARS-CoV-2 variants was high but was lower with an omicron (BA.1) variant. Vaccine-specific IFNγ+ CD4+ T cells were induced. INTERPRETATION: Immunisation with ABNCoV2 was well tolerated, safe, and resulted in a functional immune response. The data support the need for additional clinical development of ABNCoV2 as a second-generation SARS-CoV-2 vaccine. The modular cVLP platform will accelerate vaccine development, beyond SARS-CoV-2. FUNDING: EU, Carlsberg Foundation, and the Novo Nordisk Foundation.

Design of a multi-epitope Zika virus vaccine candidate - an in-silico study.

Zika virus (ZIKV), an RNA virus, rapidly spreads Aedes mosquito-borne sickness. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. In this study, to address these unmet medical needs, we aimed to design B- and T-cell candidate multi-epitope-based subunit against ZIKV using an in silico approach. In this study we applied immunoinformatics, molecular docking, and dynamic simulation assessments targeting the most immunogenic proteins; the capsid (C), envelope (E) proteins and the non-stuctural protein (NS1), described in our previous study, and which predicted immunodominant B and T cell epitopes. The final non-allergenic and highly antigenic multi-epitope was constituted of immunogenic screened-epitopes (3 CTL and 3 HTL) and the ß-defensin as an adjuvant that have been linked using EAAAK, AAY, and GPGPG linkers, respectively. The final construct containing 143 amino acids was characterized for its allergenicity, antigenicity, and physiochemical properties; and found to be safe and immunogenic with a good prediction of solubility. The existence of IFN-γ epitopes asserts the capacity to trigger strong immune responses. Subsequently, the molecular docking among vaccine and immune receptors (TLR2/TLR4) was revealed with a good binding affinity with and stable molecular interactions. Molecular dynamics simulation confirmed the stability of the complexes. Finally, the construct was subjected to in silico cloning demonstrating the efficiently of its expression in E.coli. However, this study needs the experimental validation to demonstrate vaccine safety and efficacy.Communicated by Ramaswamy H. Sarma.

A third dose SARS­CoV­2 BNT162b2 mRNA vaccine results in improved immune response in hemodialysis patients.

Background: The hemodialysis (HD) population has been a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. Advanced chronic kidney disease with uremia is associated with weaker immune response to infections and an attenuated response to vaccines. The aim of this study was to study the humoral and cellular response to the second and third doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS­CoV­2) BNT162b2 mRNA vaccine in HD patients and to follow the response over time. Methods: The patients received their first two vaccine doses from 28 December 2020 within a 4-week interval and the third dose in September 2021 and were followed-up for humoral and cellular immune response at 1) 7-15 weeks and 2) 6-8 months after dose two (no t-cell reactivity measured), and 3) 3 weeks and 4) 3 months after dose three. Fifty patients were initially enrolled, and 40 patients were followed during the entire study. Levels of COVID-19 (SARS-CoV-2) IgG antibody against the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using Enzyme-Linked ImmunoSpot (ELISPOT) technology were evaluated. Results: IgG antibodies to anti-S were detected in 35 (88%) of the 40 patients 7-15 weeks after vaccine dose two, 31 (78%) were positive, and 4 (10%) borderline. The median anti-S titer was 606 Abbott Units/milliliter (AU/mL) (interquartile range [IQR] 134-1,712). Three months after the third dose, anti-S was detected in 38 (95%) of 40 patients (P < 0.01 compared to after dose two), and the median anti-S titer was 9,910 AU/mL (IQR 2,325-26,975). Cellular reactivity was detected in 22 (55%), 34 (85%), and 28 (71%) of the 40 patients, and the median T-cell response was 9.5 (IQR 3.5-80), 51.5 (14.8-132), and 19.5 (8.8-54.2) units, respectively, for 6-8 months after dose two, 3 weeks, and 3 months after dose three. Conclusions: Our data show that a third dose of SARS­CoV­2 BNT162b2 mRNA vaccine gives a robust and improved immunological response in HD patients, but a few patients did not develop any anti-S response during the entire study, indicating the importance to monitor the vaccine response since those who do not respond could now be given monoclonal antibodies if they contract a COVID-19 infection or in the future antivirals.

Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy.

OBJECTIVES: Humoral vaccine responses to SARS-CoV-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID) following two vaccine doses. To protect these vulnerable patients against severe COVID-19 disease, a three-dose primary vaccination strategy has been implemented in many countries. The aim of this study was to evaluate humoral response and safety of primary vaccination with three doses in patients with IMID. METHODS: Patients with IMID on immunosuppressive therapy and healthy controls receiving three-dose and two-dose primary SARS-CoV-2 vaccination, respectively, were included in this prospective observational cohort study. Anti-Spike antibodies were assessed 2-4 weeks, and 12 weeks following each dose. The main outcome was anti-Spike antibody levels 2-4 weeks following three doses in patients with IMID and two doses in controls. Additional outcomes were the antibody decline rate and adverse events. RESULTS: 1100 patients and 303 controls were included. Following three-dose vaccination, patients achieved median (IQR) antibody levels of 5720 BAU/mL (2138-8732) compared with 4495 (1591-6639) in controls receiving two doses, p=0.27. Anti-Spike antibody levels increased with median 1932 BAU/mL (IQR 150-4978) after the third dose. The interval between the vaccine doses and vaccination with mRNA-1273 or a combination of vaccines were associated with antibody levels following the third dose. Antibody levels had a slower decline-rate following the third than the second vaccine dose, p<0.001. Adverse events were reported by 464 (47%) patients and by 196 (78%) controls. Disease flares were reported by 70 (7%) patients. CONCLUSIONS: This study shows that additional vaccine doses to patients with IMID contribute to strong and sustained immune-responses comparable to healthy persons vaccinated twice, and supports repeated vaccination of patients with IMID. TRIAL REGISTRATION NUMBER: NCT04798625.

Tick-Talk: Parental online discourse about TBE vaccination.

This study aimed to understand parental discourse about vaccination, and to provide guidance for communication that addresses the needs of parents. We analyzed parental discourse on child vaccination in general and tick-borne encephalitis (TBE) specifically in a Swiss parental online community. For this purpose, a data set containing 105k posts written by parents between 2007 and 2019 was analyzed using a combination of linguistic discourse analysis and qualitative content analysis. Results show that parents enter into a multidimensional decision-making process, characterized by elaborate practices of negotiation, consideration of vaccination recommendations as well as six distinct influencing thematic factors (vaccination safety, development and control, effectiveness, epidemiology, necessity, alternatives or additional prevention methods). The study shows a clear pattern of seasonality, with parents talking about TBE vaccination mostly triggered by events such as tick bites in spring and summer. From a public health perspective, the study emphasizes the need for sufficient, balanced, and tailored information about TBE vaccination. Online forums provide valuable information about what matters to parents and when, which can help public health authorities and practitioners provide information according to these concerns and enhance health literacy among parents.