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In August 2022, with mpox spreading and vaccine scarce, the Food and Drug Administration let clinics stretch the supply. Instead of a 0.5 mL injection under the skin (subcutaneous, SC), the JYNNEOS vaccine could be given as a 0.1 mL injection into the skin (intradermal, ID) — a fifth of the dose. The worry was that the intradermal route, which can leave a longer-lasting bump and was a concern for people prone to scarring or keloids, would put people off coming back for their second dose.

California checked. It didn't. Among residents whose first dose came after the change, 60.2% of those vaccinated intradermally completed the two-dose series, against 58.8% of those vaccinated under the skin. The gaps that mattered ran along age, sex and race — whichever way the first shot was given.

The vaccine and the rule change

JYNNEOS (modified vaccinia Ankara vaccine, Bavarian Nordic) is licensed as a two-dose series given 28 days apart; an interval of at least 24 days is acceptable. From May 26 to August 8, 2022, every U.S. dose was subcutaneous. On August 9, 2022, the FDA authorized the dose-sparing intradermal route, and the California Department of Public Health (CDPH) immediately recommended it — except for people with a history of keloids and people under 18.

DateCDPH guidance
August 9, 2022Use the intradermal route
October 5, 2022Expand eligibility from people exposed or at greatest risk to preexposure prophylaxis for those at risk
October 28, 2022With cases falling and supply ample, leave the route to provider and patient
November 16, 2022Offer vaccine to anyone who might be at risk and anyone who asks

The intradermal share of first doses began falling in October 2022, and from November 2022 a growing share of providers offered only the subcutaneous route.

Combination bar and line graph showing the route used by people completing the two-dose mpox vaccine series, by month of the second dose, and the share of providers offering only subcutaneous administration, California, June 2022–March 2023.

Route of the completing dose by month, and the share of providers offering only subcutaneous injection. CDC.

Who came back

CDPH analyzed adults in the California Immunization Registry who received a first dose from August 9, 2022, to March 31, 2023, counting a second dose given at least 24 days later and by April 30, 2023. Of 119,345 first doses, 83,483 (70.0%) were intradermal and 35,862 (30.0%) subcutaneous. 71,317 people (59.8%) completed the series.

GroupFirst dosesCompleted, % (any route)After SC first dose, %After ID first dose, %Odds of completing (99% CI)
All119,34559.858.860.2—
Female at birth13,44642.836.845.50.69 (0.66–0.72)
Male at birth105,36662.161.762.2reference
White, non-Hispanic53,05964.163.464.3reference
Asian, non-Hispanic14,28460.860.261.10.95 (0.91–0.99)
Multiracial or other9,69858.158.058.10.91 (0.87–0.95)
Hispanic or Latino31,27056.655.257.10.88 (0.86–0.91)
Black or African American, non-Hispanic8,82851.351.051.50.80 (0.76–0.84)
Aged 18–248,95042.941.043.70.59 (0.55–0.63)
Aged 25–3432,96351.751.351.90.71 (0.68–0.74)
Aged 35–4426,45358.959.858.40.81 (0.77–0.85)
Aged 45–5419,76764.564.364.60.89 (0.85–0.93)
Aged 55–6420,39070.069.170.40.96 (0.92–1.01)
Aged 65 and older10,82272.669.073.7reference

Completion also varied with the Healthy Places Index, which ranks each county and zip code on 25 drivers of health from 1 (least healthy) to 4 (healthiest): 56.9% in quartile 1, 62.9% in 2, 62.4% in 3 and 58.8% in 4.

In no group was completion more likely after a subcutaneous first dose. Two groups — people assigned female at birth and people 65 and older — were more likely to finish after an intradermal one.

Line chart showing the share of people completing the two-dose mpox vaccination series, by route of the first dose and month of the first dose, California, August 9, 2022–March 31, 2023.

Completion by month of the first dose and its route. In September 2022, for example, 51% of people first vaccinated subcutaneously completed the series, against 59% first vaccinated intradermally. CDC.

Why the route didn't matter

  • Intradermal doses have been shown noninferior in immune response for influenza, rabies and hepatitis B vaccines.
  • JYNNEOS effectiveness against medically attended mpox has been reported as high as 86% for two doses and 75% for one, with no significant difference by route found to date.
  • Intradermal recipients report differences in how long swelling lasts, but a CDC analysis of the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink found no significant difference in reported adverse events between the routes.

What the data can't show

The registry holds no information on behavioral risk, or on sexual orientation or gender identity. People vaccinated before August 9 — 53,892 subcutaneous doses, with 75.1% completing — cannot be compared. Falling case rates from August 2022 may have lowered interest in a second dose. The analysis covers only people who started the series, and California may not speak for other states. Overall completion among everyone whose first dose came from May 26, 2022, to March 31, 2023, was 64.5%.

What to do about it

The route was not the problem, so the authors point elsewhere: providers explaining the options and the importance of the second dose, contacting people overdue for it — especially 18- to 24-year-olds — and focused, culturally sensitive outreach by trusted messengers to the groups most affected by mpox, including Black and Hispanic people.

Sources

Based on Salih T, Vance J, Quint J, Meza B, McNitt L, Lincoln WU, Schechter R, "Demographic Disparities in Mpox Vaccination Series Completion, by Route of Vaccine Administration — California, August 9, 2022–March 31, 2023," MMWR Morbidity and Mortality Weekly Report 2023;72(30), Centers for Disease Control and Prevention and California Department of Public Health; a work of the United States government in the public domain.

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Licencia: CC0 1.0 (dominio público) · Adaptado de www.cdc.gov

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