Adverse Reactions After Intradermal Vaccination With JYNNEOS for Mpox in Korea.

In response to the Mpox domestic epidemic, South Korea initiated a nationwide vaccination program in May 2023, administering a 0.1 mL intradermal dose of JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to a high-risk group. To investigate the adverse reactions after intradermal JYNNEOS vaccination, an anonymous online survey was conducted at the National Medical Center from May 22 to July 31, 2023. Overall, 142 individuals responded. Over 80% of the respondents reported local reactions of predominantly mild severity. The predominant local reactions were pruritus, redness, and swelling; their incidence rates after the first dose were 66.2%, 48.1%, and 49.4%, respectively; the corresponding rates after the second dose were 69.2%, 60.6%, and 53.8%. Fewer respondents reported systemic symptoms. The most common systemic symptom was fatigue, the incidence rates of which after the first and second doses were 37.7% and 24.6%, respectively. Overall, the intradermally administered JYNNEOS vaccine appeared well tolerated.

Adverse drug reaction profile of third-generation smallpox vaccines used in France during the 2022 monkeypox epidemic.

Due to the start of the monkeypox epidemic in 2022, we retrospectively analyzed the adverse drug reactions (ADRs) reported in France after monkeypox vaccinations with the third-generation smallpox vaccine. Ninety-eight cases, representing 172 ADRs, were reported. ADRs were mostly expected reactogenicity reactions occurring within days after the first dose of vaccine and having a quick favorable outcome. Unexpected facial palsy and vaccination failure are discussed.

Prospective monitoring of adverse events following vaccination with Modified vaccinia Ankara - Bavarian Nordic (MVA-BN) administered to a Canadian population at risk of Mpox: A Canadian Immunization Research Network study.

MVA-BN is an orthopoxvirus vaccine that provides protection against both smallpox and mpox. In June 2022, Canada launched a publicly-funded vaccination campaign to offer MVA-BN to at-risk populations including men who have sex with men (MSM) and sex workers. The safety of MVA-BN has not been assessed in this context. To address this, the Canadian National Vaccine Safety Network (CANVAS) conducted prospective safety surveillance during public health vaccination campaigns in Toronto, Ontario and in Vancouver, British Columbia. Vaccinated participants received a survey 7 and 30 days after each MVA-BN dose to elicit adverse health events. Unvaccinated individuals from a concurrent vaccine safety project evaluating COVID-19 vaccine safety were used as controls. Vaccinated and unvaccinated participants that reported a medically attended visit on their 7-day survey were interviewed. Vaccinated participants and unvaccinated controls were matched 1:1 based on age group, gender, sex and provincial study site. Overall, 1,173 vaccinated participants completed a 7-day survey, of whom 75 % (n = 878) also completed a 30-day survey. Mild to moderate injection site pain was reported by 60 % of vaccinated participants. Among vaccinated participants 8.4 % were HIV positive and when compared to HIV negative vaccinated individuals, local injection sites were less frequent in those with HIV (48 % vs 61 %, p = 0.021), but health events preventing work/school or requiring medical assessment were more frequent (7.1 % vs 3.1 %, p = 0.040). Health events interfering with work/school, or requiring medical assessment were less common in the vaccinated group than controls (3.3 % vs. 7.1 %, p < 0.010). No participants were hospitalized within 7 or 30 days of vaccination. No cases of severe neurological disease, skin disease, or myocarditis were identified. Our results demonstrate that the MVA-BN vaccine appears safe when used for mpox prevention, with a low frequency of severe adverse events and no hospitalizations observed.

An open-label, non-randomized study investigating the safety and efficacy of smallpox vaccine, LC16, as post-exposure prophylaxis for mpox.

Mpox is an acute exanthematous disease caused by the monkeypox virus. Since May 2022, it has spread as a community-acquired infection, mainly in Europe and the United States, and urgent measures to prevent this infection were also required in Japan. In this study, we investigated the post-exposure prophylaxis of mpox and safety after inoculating the smallpox vaccine. Participants in close contact with patients with mpox were inoculated with "Freeze-dried cell culture Smallpox Vaccine LC16," within 14 days after close contact. Six cases were registered, and all the participants were inoculated. No mpox symptoms or related complications were observed in the participants for 21 days after the close contact. Adverse events due to inoculation, such as rash, fever, lymphadenopathy, and local reaction at the inoculation site (comprising erythema, swelling, induration, and pain) were observed in the participants; however, all inoculation-related events were non-severe and non-serious, and the participants recovered during the 28-day observation period. The findings of this study suggest that inoculation with LC16 is an effective post-exposure prophylaxis in individuals who had close contact with patients with mpox. Further large-scale studies are warranted to validate these findings.

A comparative analysis on serious adverse events reported for COVID-19 vaccines in adolescents and young adults.

This study aims to assess the safety profile of COVID-19 vaccines (mRNA and viral vector vaccines) in teenagers and young adults, as compared to Influenza and HPV vaccines, and to early data from Monkeypox vaccination in United States. Methods: We downloaded data from the Vaccine Adverse Event Reporting System (VAERS) and collected the following Serious Adverse Events (SAEs) reported for COVID-19, Influenza, HPV and Monkeypox vaccines: deaths, life-threatening illnesses, disabilities, hospitalizations. We restricted our analysis to the age groups 12-17 and 18-49, and to the periods December 2020 to July 2022 for COVID-19 vaccines, 2010-2019 for Influenza vaccines, 2006-2019 for HPV vaccines, June 1, 2022 to November 15, 2022 for Monkeypox vaccine. Rates were calculated in each age and sex group, based on an estimation of the number of administered doses. Results: Among adolescents the total number of reported SAEs per million doses for, respectively, COVID-19, Influenza and HPV vaccines were 60.73, 2.96, 14.62. Among young adults the reported SAEs rates for, respectively, COVID-19, Influenza, Monkeypox vaccines were 101.91, 5.35, 11.14. Overall, the rates of reported SAEs were significantly higher for COVID-19, resulting in a rate 19.60-fold higher than Influenza vaccines (95% C.I. 18.80-20.44), 4.15-fold higher than HPV vaccines (95% C.I. 3.91-4.41) and 7.89-fold higher than Monkeypox vaccine (95% C.I. 3.95-15.78). Similar trends were observed in teenagers and young adults with higher Relative Risks for male adolescents. Conclusion: The study identified a risk of SAEs following COVID-19 vaccination which was markedly higher compared to Influenza vaccination and substantially higher compared to HPV vaccination, both for teenagers and young adults, with an increased risk for the male adolescents group. Initial, early data for Monkeypox vaccination point to significantly lower rates of reported SAEs compared to those for COVID-19 vaccines. In conclusion these results stress the need of further studies to explore the bases for the above differences and the importance of accurate harm-benefit analyses, especially for adolescent males, to inform the COVID-19 vaccination campaign.

Early evaluation of the safety, reactogenicity, and immune response after a single dose of modified vaccinia Ankara-Bavaria Nordic vaccine against mpox in children: a national outbreak response.

BACKGROUND: In response to a national mpox (formerly known as monkeypox) outbreak in England, children exposed to a confirmed mpox case were offered modified vaccinia Ankara-Bavaria Nordic (MVA-BN), a third-generation smallpox vaccine, for post-exposure prophylaxis. We aimed to assess the safety and reactogenicity and humoral and cellular immune response, following the first reported use of MVA-BN in children. METHODS: This is an assessment of children receiving MVA-BN for post-exposure prophylaxis in response to a national mpox outbreak in England. All children receiving MVA-BN were asked to complete a post-vaccination questionnaire online and provide a blood sample 1 month and 3 months after vaccination. Outcome measures for the questionnaire included reactogenicity and adverse events after vaccination. Blood samples were tested for humoural, cellular, and cytokine responses and compared with unvaccinated paediatric controls who had never been exposed to mpox. FINDINGS: Between June 1 and Nov 30, 2022, 87 children had one MVA-BN dose and none developed any serious adverse events or developed mpox disease after vaccination. Post-vaccination reactogenicity questionnaires were completed by 45 (52%) of 87 children. Their median age was 5 years (IQR 5-9), 25 (56%) of 45 were male, and 22 (49%) of 45 were White. 16 (36%) reported no symptoms, 18 (40%) reported local reaction only, and 11 (24%) reported systemic symptoms with or without local reactions. Seven (8%) of 87 children provided a first blood sample a median of 6 weeks (IQR 6·0-6·5) after vaccination and five (6%) provided a second blood sample at a median of 15 weeks (14-15). All children had poxvirus IgG antibodies with titres well above the assay cutoff of OD450nm 0·1926 with mean absorbances of 1·380 at six weeks and 0·9826 at 15 weeks post-vaccination. Assessment of reactivity to 27 recombinant vaccina virus and monkeypox virus proteins showed humoral antigen recognition, primarily to monkeypox virus antigens B6, B2, and vaccina virus antigen B5, with waning of humoral responses observed between the two timepoints. All children had a robust T-cell response to whole modified vaccinia Ankara virus and a select pool of conserved pan-Poxviridae peptides. A balanced CD4+ and CD8+ T-cell response was evident at 6 weeks, which was retained at 15 weeks after vaccination. INTERPRETATION: A single dose of MVA-BN for post-exposure prophylaxis was well-tolerated in children and induced robust antibody and cellular immune responses up to 15 weeks after vaccination. Larger studies are needed to fully assess the safety, immunogenicity, and effectiveness of MVA-BN in children. Our findings, however, support its on-going use to prevent mpox in children as part of an emergency public health response. FUNDING: UK Health Security Agency.

Kaspar Hauser, the Child of Europe: Are smallpox vaccination scars the clue to a 2-century-old mystery?

We have explored the 19th century mystery of the identity of Kaspar Hauser, the so-called Child of Europe, from the perspective of the smallpox vaccination. We have highlighted the improbability that he was secretly inoculated based on the vaccination policies and methodologies applied at the time. This consideration allows for a reflection on the whole case and the importance of vaccination scars in ascertaining immunization against one of humanity's deadliest killers, especially given the recent monkeypox outbreak.

Myocarditis and pericarditis recovery following smallpox vaccine 2002-2016: A comparative observational cohort study in the military health system.

OBJECTIVES: (1) Characterize the initial clinical characteristics and long-term outcomes of smallpox vaccine-associated hypersensitivity myocarditis and pericarditis (MP) in United States service members. (2) Describe the process of case identification and adjudication using the 2003 CDC nationally defined myocarditis/pericarditis epidemiologic case definitions to include consideration of case-specific diversity and evolving evidence. BACKGROUND: Between 2002 and 2016, 2.546 million service members received a smallpox Vaccinia vaccine. Acute MP is associated with vaccinia, but the long-term outcomes have not been studied. METHODS: Records of vaccinia-associated MP reported to the Vaccine Adverse Event Reporting System by vaccination date were adjudicated using the 2003 MP epidemiologic case definitions for inclusion in a retrospective observational cohort study. Descriptive statistics of clinical characteristics, presentation, cardiac complications, and time course of clinical and cardiac recovery were calculated with comparisons by gender, diagnosis and time to recovery. RESULTS: Out of over 5000 adverse event reports, 348 MP cases who survived the acute illness, including 276 myocarditis (99.6% probable/confirmed) and 72 pericarditis (29.2% probable/confirmed), were adjudicated for inclusion in the long-term follow-up. Demographics included a median age of 24 years (IQR 21,30) and male predominance (96%). Compared to background military population, the myocarditis and pericarditis cohort had a higher percentage of white males by 8.2% (95% CI: 5.6, 10.0) and age <40 years by 4.2% (95% CI: 1.7,5.8). Long-term follow-up documented full recovery in 267/306 (87.3%) with 74.9% recovered in less than a year (median ~3 months). Among patients with myocarditis, the percentage who had a delayed time to recovery at time of last follow-up was 12.8% (95% CI: 2.1,24.7) higher in those with an acute left ventricular ejection fraction (EF) of ≤50% and 13.5% (95% CI: 2.4,25.7) higher in those with hypokinesis. Patient complications included 6 ventricular arrhythmias (2 received implanted defibrillators) and 14 with atrial arrhythmias (2 received radiofrequency ablation). Three of 6 patients (50%) diagnosed with cardiomyopathy had clinical recovery at their last follow-up date. CONCLUSIONS: Hypersensitivity myocarditis/pericarditis following the smallpox vaccine is associated with full clinical and functional ventricular recovery in over 87% of cases (74.9% <1 year). A minority of MP cases experienced prolonged or incomplete recovery beyond 1 year.

Short-term Adverse Events Following Immunization With Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) Vaccine for Mpox.

This study uses data collected by Australia's vaccine safety surveillance system to examine the adverse event profile of the modified vaccinia Ankara­Bavarian Nordic vaccine.

Cardiac events following JYNNEOS vaccination for prevention of Mpox.

The incidence of cardiac adverse events following JYNNEOS vaccination for prevention of mpox is unknown, however the Advisory Committee on Immunization Practices states that people with underlying cardiac risk factors should be counseled about the theoretical risk for myopericarditis following vaccination. We conducted a retrospective cohort study of 2,126 patients who were vaccinated with at least 1 dose of JYNNEOS vaccine and searched the Kaiser Permanente Northwest databases, including the electronic health record, to evaluate for cardiac adverse events of special interest (AESI). After physician adjudication, there were 10 confirmed cardiac AESI for an incidence of 3.1 per 1000 doses (exact 95% CI, 1.5 to 5.7), however none of these events could be directly attributed to vaccination. This retrospective cohort study of JYNNEOS vaccination for prevention of mpox identified 10 cardiac events that all had alternative explanations; and no hospitalizations or serious adverse outcomes were attributed to vaccination.

Safety and Efficacy of Post-Eradication Smallpox Vaccine as an Mpox Vaccine: A Systematic Review with Meta-Analysis.

According to the World Health Organization, 83,339 laboratory-confirmed cases, including 72 deaths, of mpox (formerly known as monkeypox), have been reported from 110 locations globally as of 20 December 2022, making the disease a public health concern. Most of the cases (56,171, 67.4%) were reported from countries in North America. Limited data on vaccine effectiveness in the current mpox outbreak are available. However, the modified vaccinia virus (smallpox vaccine) has been predicted to prevent or reduce the severity of the mpox infection. The present study of systematic review and meta-analysis aimed to evaluate the modified vaccinia vaccine's safety and efficacy on mpox by using reported randomized clinical trials. Following guidelines from the Cochrane Collaboration and PRISMA, multiple databases including PubMed, PLOS ONE, Google Scholar, British Medical Journal, and the U. S. National Library of Medicine were searched. Out of 13,294 research articles initially identified, 187 were screened after removing duplicates. Following the inclusion and exclusion criteria, the meta-analysis included ten studies with 7430 patients. Three researchers independently assessed the risk of bias in the included study. The pooled results suggest that the vaccinia-exposed group had fewer side effects when compared to the vaccinia naïve group (odds ratio: 1.66; 95% CI: 1.07-2.57; p = 0.03). Overall, the modified vaccinia has proven safe and effective in both vaccinia naïve and previously exposed groups, with higher efficacy in the previously exposed groups.

Real-world effectiveness of a single dose of mpox vaccine in males.

The recent global outbreak of the monkeypox (mpox) virus in humans was declared a public health emergency by the World Health Organization in July 2022. The smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-BN), provided as a two-dose regimen, is currently the primary vaccine utilized against mpox. However, the efficacy of MVA-BN against mpox has never been demonstrated in clinical trials to date. Due to the limited supply of vaccines, the World Health Organization has recommended prioritizing the vaccination of high-risk groups. We evaluated the real-world effectiveness of a single, subcutaneous dose of MVA-BN in this observational, retrospective cohort study, which included the analysis of electronic health records of all members of Clalit Health Services eligible for the vaccine on 31 July 2022. We used a Cox proportional hazards regression model with time-dependent covariates to estimate the association between vaccination and mpox while adjusting for sociodemographic and clinical risk factors. In an analysis of 2,054 male individuals who met vaccine eligibility criteria, 1,037 (50%) were vaccinated during the study recruitment period and completed at least 90 d of follow-up. During the study period, 5 and 16 infections were confirmed in vaccinated and unvaccinated individuals, respectively. The adjusted vaccine effectiveness was estimated at 86% (95% confidence interval, 59-95%). Our results suggest that a single dose of subcutaneous MVA-BN in this high-risk cohort is associated with a significantly lower risk of MPXV infection.

A randomized phase 3 trial to assess the immunogenicity and safety of 3 consecutively produced lots of freeze-dried MVA-BN® vaccine in healthy adults.

Since vaccination remains the only effective protection against orthopox virus-induced diseases such as smallpox or monkeypox, the strategic use and stockpiling of these vaccines remains of significant public health importance. The approved liquid-frozen formulation of Bavarian Nordic's Modified Vaccinia Ankara (MVA-BN) smallpox vaccine has specific cold-chain requirements, while the freeze-dried (FD) formulation of this vaccine provides more flexibility in terms of storage conditions and shelf life. In this randomized phase 3 trial, the immunogenicity and safety of 3 consecutively manufactured lots of the FD MVA-BN vaccine was evaluated. A total of 1129 healthy adults were randomized to 3 treatment groups (lots 1 to 3) and received 2 vaccinations 4 weeks apart. For both neutralizing and total antibodies, a robust increase of geometric mean titer (GMT) was observed across all lot groups 2 weeks following the second vaccination, comparable to published data. For the primary results, the ratios of the neutralizing antibody GMTs between the lot group pairs ranged from 0.936 to 1.115, with confidence ratios well within the pre-specified margin of equivalence. Results for total antibodies were similar. In addition, seroconversion rates were high across the 3 lots, ranging between 99.1 % and 99.7 %. No safety concerns were identified; particularly, no inflammatory cardiac disorders were detected. The most common local solicited adverse events (AEs) reported across lot groups were injection site pain (87.2%) and erythema (73.2%), while the most common general solicited adverse events were myalgia, fatigue, and headache in 40.6% to 45.5% of all participants, with no meaningful differences among the lot groups. No related serious AEs were reported. In conclusion, the data demonstrate consistent and robust immunogenicity and safety results with a freeze-dried formulation of MVA-BN. Clinical Trial Registry Number: NCT03699124.

A review of monkeypox infection during pregnancy.

The present study aimed to review monkeypox infection during pregnancy: its epidemiology and etiology, transmission, clinical manifestations and complications, diagnosis, management, antenatal testing and delivery, prevention, awareness, and recommendations. Monkeypox can spread via vertical transmission. The usual clinical symptoms include fever, rash (vesicles, crust), new genital lesions, or sore throat. It is only recommended to use cidofovir in pregnant patients when they are severely infected with monkeypox. All woman who are at high risk of exposure for monkeypox need to be vaccinated with the smallpox vaccine regardless of their pregnancy status. Monitoring includes regular non-stress test monitoring in addition to ultrasound performed at various stages of pregnancy. High index of suspicion, informed physicians, reporting of cases, and support of research are all needed for the management of monkeypox infection during pregnancy.