Evidence to Recommendations (EtR) Framework for Use of JYNNEOS in Persons Aged ¡Ý18 Years at Risk for Mpox During the Ongoing Clade IIb Outbreak

• Vaccine performance: Comparison of incidence between vaccinated and unvaccinated persons in 43 U.S. jurisdictions showed mpox incidence among unvaccinated 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
• Population-based, adjusted measures of vaccine effectiveness (VE) using electronic medical records: Nationwide, U.S. case-control study with 1:4 ratio of cases matched to controls; adjusted VE was 35.8% (95% CI: 22.1-47.1%) for one dose and 66.0% (95% CI: 47.7-78%) for 2 doses, regardless of vaccination route
• Population-based, adjusted measures of VE using case-control studies:  1) Case-control study of adult MSM (18-49 years of age) in 12 U.S. jurisdictions; adjusted (adjusted for week of diagnosis, region, age, race/ethnicity) VE was 76% (95% CI:  48-49%) for 2 doses (interim results) 2) New York State case-control study of adult male mpox cases matched to sexually transmitted infection controls; adjusted VE was 68% (95% CI:  25-86%) for one dose and 89% (95% CI:  44-98%) for 2 doses (preliminary results)
• PEP effectiveness and infections following single dose: NYC: Cohort study of individuals with high-risk exposure; VE was 78% (CI 50-91) with PEP 0-14 days after last exposure and 73% (CI 31-91) with PEP 0-14 days after first exposure using multivariable regression. However when using Target trial methodology, VE was 19% (CI -54-57) with PEP 0-14 days after last exposure and -7% (CI -144-53) with PEP 0-14 days after first exposure.

• During May 22, 2022 to January 13, 2023, a total of 1,125,168 JYNNEOS vaccine doses were administered. CDC monitored JYNNEOS safety using VAERS, V-safe, and VSD for vaccine recipients of all ages. Most common AEs reported were nonserious and included injection site reactions, consistent with prelicensure studies. These were reported at similar rates for doses received by intradermal and subcutaneous administration. Serious adverse events were rare among adults.
• No new safety signals have been identified since the pre-licensure studies.  The adverse events most commonly reported to VAERS have been injection site symptoms (i.e., redness, swelling, pain, itching).

• During August to November 2022, >85% of respondents in the American Transformative HIV Study (AMETHYST) were interested in vaccine, and uptake doubled from August to September.
• During August to December 2022, 50% of Porter-Novelli survey responders who identified as LGBTP+ felt the vaccination is important to protect from mpox
• During October to November 2022, >70% of MSM in a San Francisco survey of persons experiencing homelessness reported that they would accept or have accepted vaccination
• During October-December 2022, an American Men’s Interest Survey (AMIS) showed that those who were concerned about mpox were 3.5 times more likely to be vaccinated.
• The CDC-DC PEP++ Study was a CDC and DC Health collaboration to follow a cohort of persons at elevated risk of mpox exposure in Washington D.C., who presented for JYNNEOS vaccination, August 2022-October 2022.  The survey involved 866 adults; >85% agreed or strongly agreed that vaccines for mpox should be available to anyone who wants the vaccine.  A total of 82% were likely or very likely to get a third dose if it was recommended.
• Qualitative interviews among adults presenting for JYNNEOS vaccine in Washington D.C during August 2022 to September 2022 showed that many participants were grateful that LBTQ+ were given priority vaccine access.  This suggests there is interest in vaccine during the ongoing outbreak.
• Early studies indicated conflicting feelings about receiving JYNNEOS:  1) Curtis et al:  Survey with 320 persons, primarily MSM living in Illinois and at risk for mpox in September 2022.  24.1% received 2 vaccine doses, 27.5% received one dose, 47.5% no doses. Persons who were vaccinated were more likely to have higher education, know someone with mpox, express concern about their safety, and be less likely to report recent food insecurity.  2) Turpin et al. Qualitative interviews with 24 Black MSM attending HIV prevention-related events in greater D.C. area, May 2022.  There was lack of availability of mpox vaccines was a common concern suggesting interest and vaccine hesitancy was common.
• Later studies:  1) In May 2023, there was a state of vaccine confidence report from CDC.  During May 2023, there was an mpox cluster identified in Chicago affecting persons who received 2 doses of the JYNNEOS vaccine.  A review of mpox-related discussions on 23 news and social media outlets in the Chicago area was performed and findings were as follows:  mpox vaccine hesitancy among the general public and LGBTQ affiliated groups were noted.  Questions were raised about the effectiveness and safety of the vaccine (e.g., sentiment expressed that vaccine is experimental) and distrust in reporting (e.g., suspicion that mpox reporting is exaggerated). 2) Interviews with 18 patients associated with the mpox cluster in Chicago occurred in May 2023. People interviewed included fully vaccinated, partially vaccinated, and unvaccinated persons with mpox.  Most stated they would recommend mpox vaccine to others.  Some indicated they assumed the vaccine would prevent infection but most did believe that the vaccine was effective in reducing the severity of their illness compared to their friends who had mpox at the start of the outbreak (i.e., before vaccine was more readily available). Unvaccinated persons reported that they had initial interest in the vaccine when supply was limited but they were unable to receive it at that time.  They reported they did not continue to seek the vaccine because when case counts decreased, they assumed their risk was low. 3) An online focus group was performed by CDC to develop communication material in July 2023.  The session was conducted with 52 persons who identified as men, were unvaccinated for mpox and never diagnosed with mpox, 18-45 years of age, and had sex with 2 or more men within the previous 6 months.  The participant demographics included an average age of 30-34 years, 48% Black, 37% White, 27% Hispanic/Latino, and 75% self-reported gay (21% bisexual). Exposure to the communication materials increased interest in receiving the mpox vaccine. The risk presented to the participants and the protection to the community that vaccination would provide were considered motivating. Many of the people who had been disinterested in the vaccine became interested by the conclusion; however, there were still some persons who did not change their minds.

• SermoA is an online community of >1.3 million clinicians. During July 31-August 1, 2022, survey results of U.S. clinicians (n= 415) showed 69% felt U.S. did not have enough mpox vaccine to handle the outbreak. On September 12, 2022, the survey among 62 U.S. clinicians showed 66% had treated at least one patient with mpox, 76% knew where a patient could get the JYNNEOS vaccination, and 86% wanted to be able to provide vaccination in their office.
• During the peak of the outbreak, health departments requested JYNNEOS and organized vaccination campaigns. Jurisdictions had ordered 70% of their allocations by February 2023.
• A vaccine equity pilot program was established. This enabled jurisdictions to request more than their allotted amount of JYNNEOS vaccine.  It was established to support innovative ways to address vaccination disparities, encourage vaccination coordination between health departments and community-based organizations, and promote innovation to strengthen existing vaccination infrastructure.  A total of 28 programs were established involving 15 jurisdictions and ~25,000 doses were administered as of February 2023.
• A Porter-Novelli Survey of 102 pediatricians and 104 family practice physicians in August 2023. Of these, 85% of FP and 88% of pediatricians cared for children 12-17 years of age; 70% of FP and 60% of pediatricians cared for patients 18+ years of age.  54% had >1500 patients in their practice and a majority (75%) were in private practice with 14% in Federally Qualified Health Centers. When asked whether they would prefer to provide the mpox vaccine within their practice, Family Practitioners more often strongly or somewhat preferred providing the vaccine within their own practice.  Pediatricians were supportive of the vaccine but preferred referring patients to places outside of their practice.
• In general, a shift has occurred in sites of vaccination as evidenced by surveillance data.  Public health clinics were the site of vaccination at the start of the outbreak, but this has shifted to medical centers over time.  Public health providers administered 40% of all vaccines through March 2023, medical providers administered an increasing proportion of vaccines in 2023, and pharmacies at that time consistently provided 3-4% of all vaccines. From 2022 to 2023, there were statistically significant increases in vaccines provided by primary care offices, Federally Qualified Health Centers, and other health centers.
• An online focus group was performed by CDC to understand provider knowledge, attitudes, and practices related to service delivery, including those specific to mpox. Of the 41 healthcare providers, 68% had never managed an mpox case, 34% believed mpox is a threat to public health, 32% reported mpox is important to their patient populations, and 51% believed that mpox services should be integrated into standard care to increase access to vaccines, improve education and awareness about mpox for patients, and ensure comprehensive STI screening and testing.

In the future, it is possible that the vaccine will be commercialized but if so, there will be unknown costs associated with commercialization

A routine recommendation will facilitate 1:1 counseling and information sharing in the privacy of a clinic; vaccine recommendation from a clinician is associated with increased vaccine uptake.

• During September 2023, $5,000,000 allocated to community-based organizations (CBOs) to advance mpox prevention and vaccination effortsB. CBOs were essential to increasing vaccination coverage among those at highest risk and served a pivotal role in 2022. 42 CBOs were funded during the vote.
• If commercialize, there may be an impact on primary sites of vaccination

A routine recommendation might facilitate broad acceptance of vaccination (e.g., by insurance companies, patients) because endorsement by ACIP only occurs after rigorous review