JYNNEOS Vaccine for Mpox.

This JAMA Patient Page describes the eligibility, safety and effectiveness, and administration procedure for the JYNNEOS vaccine for mpox infection.

Effectiveness of JYNNEOS Vaccine Against Diagnosed Mpox Infection - New York, 2022.

In 2022, an international Monkeypox virus outbreak, characterized by transmission primarily through sexual contact among gay, bisexual, and other men who have sex with men (MSM), resulted in 375 monkeypox (mpox) cases in the state of New York outside of New York City (NYC).*,† The JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), licensed by the U.S. Food and Drug Administration (FDA) against mpox as a 2-dose series, with doses administered 4 weeks apart,§ was deployed in a national vaccination campaign.¶ Before this outbreak, evidence to support vaccine effectiveness (VE) against mpox was based on human immunologic and animal challenge studies (1-3). New York State Department of Health (NYSDOH) conducted a case-control study to estimate JYNNEOS VE against diagnosed mpox in New York residents outside of NYC, using data from systematic surveillance reporting. A case-patient was defined as a man aged ≥18 years who received a diagnosis of mpox during July 24-October 31, 2022. Contemporaneous control patients were men aged ≥18 years with diagnosed rectal gonorrhea or primary syphilis and a history of male-to-male sexual contact, without mpox. Case-patients and control patients were matched to records in state immunization systems. JYNNEOS VE was estimated as 1 - odds ratio (OR) x 100, and JYNNEOS vaccination status (vaccinated versus unvaccinated) at the time of diagnosis was compared, using conditional logistic regression models that adjusted for week of diagnosis, region, patient age, and patient race and ethnicity. Among 252 eligible mpox case-patients and 255 control patients, the adjusted VE of 1 dose (received ≥14 days earlier) or 2 doses combined was 75.7% (95% CI = 48.5%-88.5%); the VE for 1 dose was 68.1% (95% CI = 24.9%-86.5%) and for 2 doses was 88.5% (95% CI = 44.1%-97.6%). These findings support recommended 2-dose JYNNEOS vaccination consistent with CDC and NYSDOH guidance.

Demographics and Health Beliefs of Black Gay, Bisexual, and Other Sexual Minority Men Receiving a Mpox Vaccination in the United States.

An outbreak of mpox virus (MPV) among humans in the United States (U.S.) was described in May 2022. This outbreak disproportionately affects Black and Hispanic sexual minority men (SMM) and these groups have lower rates of vaccination compared to Whites. Between July and August 2022, a partnership between a nonprofit and two local health departments successfully designed and implemented a community intervention to administer MPV vaccines to Black SMM in the Washington D.C. metropolitan area. We administered a quantitative survey to 178 respondents across four vaccinations clinics. We found that study participants had high socioeconomic status, high levels of anticipated MPV stigma, and were relatively skeptic about MPV. We demonstrated how a partnership between an urban nonprofit and government agency can facilitate quick and effective dissemination of a community intervention in a relatively low cost manner.

Safety Monitoring of JYNNEOS Vaccine During the 2022 Mpox Outbreak - United States, May 22-October 21, 2022.

JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended in the United States for persons exposed to or at high risk for exposure to Monkeypox virus during the 2022 monkeypox (mpox) outbreak (1). JYNNEOS is a live, nonreplicating viral vaccine licensed for the prevention of smallpox and mpox in adults aged ≥18 years, administered as a 0.5-mL 2-dose series given 28 days apart by subcutaneous injection (2). On August 9, 2022, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for administration of 0.1 mL doses by intradermal injection for adults aged ≥18 years as a strategy to increase vaccine supply, and administration of 0.5 mL doses subcutaneously for persons aged <18 years (3). During May 22-October 21, 2022, a total of 987,294 JYNNEOS vaccine doses were administered in the United States. CDC has monitored JYNNEOS vaccine safety using the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for vaccine recipients of all ages, and through single-patient emergency Investigational New Drug (EIND) procedures for persons aged <18 years vaccinated before August 9, 2022. The most common adverse health events reported to VAERS for adults were nonserious and included injection site reactions, which was consistent with the prelicensure studies. Adverse health events were reported at similar rates for doses received by intradermal and subcutaneous administration. Serious adverse events were rare in adults, and no serious adverse events have been identified among persons aged <18 years. Overall, postlicensure and postauthorization surveillance to date support JYNNEOS vaccine safety.

Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated Persons - 43 U.S. Jurisdictions, July 31-October 1, 2022.

As of October 28, 2022, a total of 28,244* monkeypox (mpox) cases have been reported in the United States during an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply† (3). A previous comparison of mpox incidence during July 31-September 3, 2022, among unvaccinated, but vaccine-eligible men aged 18-49 years and those who had received ≥1 JYNNEOS vaccine dose in 32 U.S. jurisdictions, found that incidence among unvaccinated persons was 14 times that among vaccinated persons (95% CI = 5.0-41.0) (4). During September 4-October 1, 2022, a total of 205,504 persons received JYNNEOS vaccine dose 2 in the United States.§ To further examine mpox incidence among persons who were unvaccinated and those who had received either 1 or 2 JYNNEOS doses, investigators analyzed data on 9,544 reported mpox cases among men¶ aged 18-49 years during July 31-October 1, 2022, from 43 U.S. jurisdictions,** by vaccination status. During this study period, mpox incidence (cases per 100,000 population at risk) among unvaccinated persons was 7.4 (95% CI = 6.0-9.1) times that among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier and 9.6 (95% CI = 6.9-13.2) times that among persons who received dose 2 ≥14 days earlier. The observed distribution of subcutaneous and intradermal routes of administration of dose 1 among vaccinated persons with mpox was not different from the expected distribution. This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously. The degree and durability of such protection remains unclear. Persons eligible for mpox vaccination should receive the complete 2-dose series to optimize strength of protection†† (5).

Mpox vaccination willingness, determinants, and communication needs in gay, bisexual, and other men who have sex with men, in the context of limited vaccine availability in the Netherlands (Dutch Mpox-survey).

Introduction: In the 2022 multicountry mpox (formerly named monkeypox) outbreak, several countries offered primary preventive vaccination (PPV) to people at higher risk for infection. We study vaccine acceptance and its determinants, to target and tailor public health (communication-) strategies in the context of limited vaccine supply in the Netherlands. Methods: Online survey in a convenience sample of gay, bisexual and other men who have sex with men, including transgender persons (22/07-05/09/2022, the Netherlands). We assessed determinants for being (un)willing to accept vaccination. We used multivariable multinominal regression and logistic regression analyses, calculating adjusted odds ratios (aOR) and 95 percent confidence-intervals. An open question asked for campaigning and procedural recommendations. Results: Of respondents, 81.5% (n = 1,512/1,856) were willing to accept vaccination; this was 85.2% (799/938) in vaccination-eligible people and 77.7% (713/918) in those non-eligible. Determinants for non-acceptance included: urbanization (rural: aOR:2.2;1.2-3.7; low-urban: aOR:2.4;1.4-3.9; vs. high-urban), not knowing mpox-vaccinated persons (aOR:2.4;1.6-3.4), and lack of connection to gay/queer-community (aOR:2.0;1.5-2.7). Beliefs associated with acceptance were: perception of higher risk/severity of mpox, higher protection motivation, positive outcome expectations post vaccination, and perceived positive social norms regarding vaccination. Respondents recommended better accessible communication, delivered regularly and stigma-free, with facts on mpox, vaccination and procedures, and other preventive options. Also, they recommended, "vaccine provision also at non-clinic settings, discrete/anonymous options, self-registration" to be vaccinated and other inclusive vaccine-offers (e.g., also accessible to people not in existing patient-registries). Conclusion: In the public health response to the mpox outbreak, key is a broad and equitable access to information, and to low-threshold vaccination options for those at highest risk. Communication should be uniform and transparent and tailored to beliefs, and include other preventive options. Mpox vaccine willingness was high. Public health efforts may be strengthened in less urbanized areas and reach out to those who lack relevant (community) social network influences.

Vaccine hesitancy and other obstacles to COVID-19 control: lessons from smallpox.

The world confronts today a disease which was unknown as recently as early 2019. Now that there is a safe and effective vaccine against COVID-19, lessons can usefully be drawn from previous well documented vaccination efforts. Of these, the best documented and most successful is the Smallpox Eradication Program (SEP). A review was made of publications by major players in smallpox eradication, respecting the important differences between the disease, this review revealed several points of connection. Cultural factors loomed large both in the eradication of smallpox and progress, to date, in the control of COVID-19. Other points of similarity included political commitment, the set-up of strong surveillance mechanisms, and assurance of uniformly high quality vaccines tested and approved by the World Health Organization. The future of COVID-19 control depends, in part, on lessons learned from previous vaccination efforts. A review of those efforts will avoid repetition of past errors and permit adoption of best practices from the past. Such analyses must, of course, respect the important differences between COVID-19 and smallpox.

A human recombinant analogue to plasma-derived vaccinia immunoglobulin prophylactically and therapeutically protects against lethal orthopoxvirus challenge.

Orthopoxviruses such as variola and monkeypox viruses continue to threaten the human population. Monkeypox virus is endemic in central and western Africa and outbreaks have reached as far as the U.S. Although variola virus, the etiologic agent of smallpox, has been eradicated by a successful vaccination program, official and likely clandestine stocks of the virus exist. Moreover, studies with ectromelia virus (the etiological agent of mousepox) have revealed that IL-4 recombinant viruses are significantly more virulent than wild-type viruses even in mice treated with vaccines and/or antivirals. For these reasons, it is critical that antiviral modalities are developed to treat these viruses should outbreaks, or deliberate dissemination, occur. Currently, 2 antivirals (brincidofovir and tecovirimat) are in the U.S. stockpile allowing for emergency use of the drugs to treat smallpox. Both antivirals have advantages and disadvantages in a clinical and emergency setting. Here we report on the efficacy of a recombinant immunoglobulin (rVIG) that demonstrated efficacy against several orthopoxviruses in vitro and in vivo in both a prophylactic and therapeutic fashion. A single intraperitoneal injection of rVIG significantly protected mice when given up to 14 days before or as late as 6 days post challenge. Moreover, rVIG reduced morbidity, as measured by weight-change, as well as several previously established biomarkers of disease. In rVIG treated mice, we found that vDNA levels in blood were significantly reduced, as was ALT (a marker of liver damage) and infectious virus levels in the liver. No apparent adverse events were observed in rVIG treated mice, suggesting the immunoglobulin is well tolerated. These findings suggest that recombinant immunoglobulins could be candidates for further evaluation and possible licensure under the FDA Animal Rule.

[Development and use of vaccines from the 18th century to the SARS-CoV 2 period].

This review is about the development and use of vaccines from the early smallpox vaccine in the 18th century to the forthcoming SARS-CoV 2 vaccines. Immunisations have been of paramount importance for childhood mortality and public health in general, but some obstacles have also been encountered such as vaccine failures and vaccine scepticism. This calls for continued emphasis on large phase three studies not only for demonstration of efficacy but also for safety and possible side effects. The rapid approval of SARS-CoV 2 vaccines requires special attention.

Human Antibody Responses Following Vaccinia Immunization Using Protein Microarrays and Correlation With Cell-Mediated Immunity and Antibody-Dependent Cellular Cytotoxicity Responses.

BACKGROUND: There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. METHODS: A total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC group), or liquid MVA given intradermally (liquid-ID group) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), interferon-γ release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with plaque reduction neutralization titer (PRNT), enzyme-linked immunosorbent assay, ADCC, and ELISPOT results. RESULTS: MVA elicited significant microarray antibody responses to 15 of 224 antigens, mostly virion membrane proteins, at day 28 or 42, particularly WR113/D8L and WR101H3L. In the liquid-SC group, responses to 9 antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three were correlated in the liquid-ID group. No significant correlations were observed with ELISPOT responses. In the liquid-ID group, WR052/F13L, a membrane glycoprotein, correlated with ADCC responses. CONCLUSIONS: MVA elicited antibodies to 15 vaccinia strain antigens representing virion membrane. Antibody responses to 2 proteins strongly increased and significantly correlated with increases in PRNT. Responses to these proteins are potential correlates of protection and may serve as immunogens for future vaccine development. CLINICAL TRIALS REGISTRATION: NCT00914732.

Serological Immunity to Smallpox in New South Wales, Australia.

The re-emergence of smallpox is an increasing and legitimate concern due to advances in synthetic biology. Vaccination programs against smallpox using the vaccinia virus vaccine ceased with the eradication of smallpox and, unlike many other countries, Australia did not use mass vaccinations. However, vaccinated migrants contribute to population immunity. Testing for vaccinia antibodies is not routinely performed in Australia, and few opportunities exist to estimate the level of residual population immunity against smallpox. Serological data on population immunity in Australia could inform management plans against a smallpox outbreak. Vaccinia antibodies were measured in 2003 in regular plasmapheresis donors at the Australian Red Cross Blood Service from New South Wales (NSW). The data were analysed to estimate the proportion of Australians in NSW with detectable serological immunity to vaccinia. The primary object of this study was to measure neutralising antibody titres against vaccinia virus. Titre levels in donor samples were determined by plaque reduction assay. To estimate current levels of immunity to smallpox infection, the decline in geometric mean titres (GMT) over time was projected using two values for the antibody levels estimated on the basis of different times since vaccination. The results of this study suggest that there is minimal residual immunity to the vaccinia virus in the Australian population. Although humoral immunity is protective against orthopoxvirus infections, cell-mediated immunity and immunological memory likely also play roles, which are not quantified by antibody levels. These data provide an immunological snapshot of the NSW population, which could inform emergency preparedness planning and outbreak control, especially concerning the stockpiling of vaccinia vaccine.

Three different paths to introduce the smallpox vaccine in early 19th century United States.

The ancient technique of variolation (inoculation of the smallpox) which was introduced in the United States in 1721 was replaced by vaccination (inoculation of the cowpox) soon after the procedure was published by Edward Jenner in 1798. Benjamin Waterhouse is recognized as the introducer of smallpox vaccination in the United States having conducted the first vaccination in Boston on 8 July 1800, although other American physicians also played an important role in extending vaccination in the East Coast of the United States. A different route of introduction brought the smallpox vaccine from Mexico to New Mexico (March 1805) and Texas (April 1806) which at that time where part of the Viceroyalty of New Spain. The vaccine was brought to California in 1817 by Russian merchants who obtained it in Peru, where the vaccine had arrived in 1806 with the Spanish Philanthropic Expedition of the Vaccine. It took almost 150 years of vaccination efforts before the last natural outbreak of smallpox occurred in the United States in 1949.

The Falconi's needle against anti-vaccination: A minimally invasive tool in the nineteenth century.

The history of Giovanni Falconi's career and his vaccination campaigns is two hundred years old. It is however very relevant today because of the widespread negative social opinion against vaccination at that time, opinions which seem to have re-emerged even in the current century. In his very important role of "Vaccine Conservator" (a sort of national supervisor for the quality of vaccinations), he clashed with the prejudice of the people and with the anti-scientific attitudes of some of his illustrious colleagues. He investigated how to simplify the procedure with a smallpox needle that became known as "Falconi's Needle" or "Falconian Needle". Falconi also made several experiments on smallpox vaccine preparation and was a supporter of the use of "animal" and "humanized" formulas despite the prejudice regarding the latter. Due to his profound anatomical knowledge and the strength of mind that characterized him, he was able to follow evidence-based scientific principles in his methods. Thanks to this he managed to convince people not to oppose vaccinations. He also succeeded in bringing the number of vaccinated people to exceed the number of newborns, a great achievement that led to remarkable progress in Italy and the rescue of thousands of lives throughout Europe. Unfortunately, it was not possible to find a copy of this instrument, which required the author to have the needle reconstructed.