Progress Toward Equitable Mpox Vaccination Coverage: A Shortfall Analysis - United States, May 2022-April 2023.

More than 30,000 monkeypox (mpox) cases were reported in the United States during the 2022 multinational outbreak; cases disproportionately affected gay, bisexual, and other men who have sex with men (MSM). Substantial racial and ethnic disparities in incidence were also reported (1). The national mpox vaccination strategy* emphasizes that efforts to administer the JYNNEOS mpox vaccine should be focused among the populations at elevated risk for exposure to mpox (2). During May 2022-April 2023, a total of 748,329 first JYNNEOS vaccine doses (of the two recommended) were administered in the United States.† During the initial months of the outbreak, lower vaccination coverage rates among racial and ethnic minority groups were reported (1,3); however, after implementation of initiatives developed to expand access to mpox vaccination,§ coverage among racial and ethnic minority groups increased (1,4). A shortfall analysis was conducted to examine whether the increase in mpox vaccination coverage was equitable across all racial and ethnic groups (5). Shortfall was defined as the percentage of the vaccine-eligible population that did not receive the vaccine (i.e., 100% minus the percentage of the eligible population that did receive a first dose). Monthly mpox vaccination shortfalls were calculated and were stratified by race and ethnicity; monthly percent reductions in shortfall were also calculated compared with the preceding month's shortfall (6). The mpox vaccination shortfall decreased among all racial and ethnic groups during May 2022-April 2023; however, based on analysis of vaccine administration data with race and ethnicity reported, 66.0% of vaccine-eligible persons remained unvaccinated at the end of this period. The shortfall was largest among non-Hispanic Black or African American (Black) (77.9%) and non-Hispanic American Indian or Alaska Native (AI/AN) (74.5%) persons, followed by non-Hispanic White (White) (66.6%) and Hispanic or Latino (Hispanic) (63.0%) persons, and was lowest among non-Hispanic Asian (Asian) (38.5%) and non-Hispanic Native Hawaiian and other Pacific Islander (NH/OPI) (43.7%) persons. The largest percentage decreases in the shortfall were achieved during August (17.7%) and September (8.5%). However, during these months, smaller percentage decreases were achieved among Black persons (12.2% and 4.9%, respectively), highlighting the need for a focus on equity for the entirety of a public health response. Achieving equitable progress in JYNNEOS vaccination coverage will require substantial decreases in shortfalls among Black and AI/AN persons.

JYNNEOS Vaccination Coverage Among Persons at Risk for Mpox - United States, May 22, 2022-January 31, 2023.

From May 2022 through the end of January 2023, approximately 30,000 cases of monkeypox (mpox) have been reported in the United States and >86,000 cases reported internationally.* JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended for subcutaneous administration to persons at increased risk for mpox (1,2) and has been demonstrated to provide protection against infection (3-5). To increase the total number of vaccine doses available, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) on August 9, 2022, recommending administration of the vaccine intradermally (0.1 mL per dose) for persons aged ≥18 years who are recommended to receive it (6); intradermal administration can generate an equivalent immune response to that achieved through subcutaneous injection using approximately one fifth the subcutaneous dose (7). CDC analyzed JYNNEOS vaccine administration data submitted to CDC from jurisdictional immunization information systems (IIS)† to assess the impact of the EUA and to estimate vaccination coverage among the population at risk for mpox. During May 22, 2022-January 31, 2023, a total of 1,189,651 JYNNEOS doses (734,510 first doses and 452,884 second doses)§ were administered. Through the week of August 20, 2022, the predominant route of administration was subcutaneous, after which intradermal administration became predominant, in accordance with FDA guidance. As of January 31, 2023, 1-dose and 2-dose (full vaccination) coverage among persons at risk for mpox is estimated to have reached 36.7% and 22.7%, respectively. Despite a steady decline in mpox cases from a 7-day daily average of more than 400 cases on August 1, 2022, to five cases on January 31, 2023, vaccination for persons at risk for mpox continues to be recommended (1). Targeted outreach and continued access to and availability of mpox vaccines to persons at risk are important to help prevent and minimize the impact of a resurgence of mpox.

Racial and Ethnic Disparities in Mpox Cases and Vaccination Among Adult Males - United States, May-December 2022.

As of December 31, 2022, a total of 29,939 monkeypox (mpox) cases* had been reported in the United States, 93.3% of which occurred in adult males. During May 10-December 31, 2022, 723,112 persons in the United States received the first dose in a 2-dose mpox (JYNNEOS)† vaccination series; 89.7% of these doses were administered to males (1). The current mpox outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and racial and ethnic minority groups (1,2). To examine racial and ethnic disparities in mpox incidence and vaccination rates, rate ratios (RRs) for incidence and vaccination rates and vaccination-to-case ratios were calculated, and trends in these measures were assessed among males aged ≥18 years (males) (3). Incidence in males in all racial and ethnic minority groups except non-Hispanic Asian (Asian) males was higher than that among non-Hispanic White (White) males. At the peak of the outbreak in August 2022, incidences among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) males were higher than incidence among White males (RR = 6.9 and 4.1, respectively). Overall, vaccination rates were higher among males in racial and ethnic minority groups than among White males. However, the vaccination-to-case ratio was lower among Black (8.8) and Hispanic (16.2) males than among White males (42.5) during the full analytic period, indicating that vaccination rates among Black and Hispanic males were not proportionate to the elevated incidence rates (i.e., these groups had a higher unmet vaccination need). Efforts to increase vaccination among Black and Hispanic males might have resulted in the observed relative increased rates of vaccination; however, these increases were only partially successful in reducing overall incidence disparities. Continued implementation of equity-based vaccination strategies is needed to further increase vaccination rates and reduce the incidence of mpox among all racial and ethnic groups. Recent modeling data (4) showing that, based on current vaccination coverage levels, many U.S. jurisdictions are vulnerable to resurgent mpox outbreaks, underscore the need for continued vaccination efforts, particularly among racial and ethnic minority groups.

The type I restriction endonuclease EcoR124I, couples ATP hydrolysis to bidirectional DNA translocation.

Type I restriction endonuclease holoenzymes contain methylase (M), restriction (R) and specificity (S) subunits, present in an M2:R2:S1 stoichiometry. These enzymes bind to specific DNA sequences and translocate dsDNA in an ATP-dependent manner toward the holoenzyme anchored at the recognition sequence. Once translocation is impeded, DNA restriction, which functions to protect the host cell from invading DNA, takes place. Translocation and DNA cleavage are afforded by the two diametrically opposed R-subunits. To gain insight into the mechanism of translocation, a detailed characterization of the ATPase activity of EcoR124I was done. Results show that following recognition sequence binding, ATP hydrolysis-coupled, bidirectional DNA translocation by EcoR124I ensues, with the R-subunits transiently disengaging, on average, every 515 bp. Macroscopic processivity of 2031(+/-184)bp is maintained, as the R-subunits remain in close proximity to the DNA through association with the methyltransferase. Transient uncoupling of ATP hydrolysis from translocation results in 3.1(+/-0.4) ATP molecules being hydrolyzed per base-pair translocated per R-subunit. This is the first clear demonstration of the coupling of ATP hydrolysis to dsDNA translocation, albeit inefficient. Once translocation is impeded on supercoiled DNA, the DNA is cleaved. DNA cleavage inactivates the EcoR124I holoenzyme partially and reversibly, which explains the stoichiometric behaviour of type I restriction enzymes. Inactivated holoenzyme remains bound to the DNA at the recognition sequence and immediately releases the nascent ends. The release of nascent ends was demonstrated using a novel, fluorescence-based, real-time assay that takes advantage of the ability of the Escherichia coli RecBCD enzyme to unwind restricted dsDNA. The resulting unwinding of EcoR124I-restricted DNA by RecBCD reveals coordination between the restriction-modification and recombination systems that functions to destroy invading DNA efficiently. In addition, we demonstrate the displacement of EcoR124I following DNA cleavage by the translocating RecBCD enzyme, resulting in the restoration of catalytic function to EcoR124I.