A fifth of a dose, into the skin, and it worked

By 31 March 2023 the United States had reported **more than 30,000 mpox
cases** in an outbreak that **disproportionately affected gay, bisexual and
other men who have sex with men, and transgender people.**

JYNNEOS was approved in 2019 as **two 0.5 mL subcutaneous doses four weeks
apart**. There was not enough of it. So on **9 August 2022 the FDA issued an
Emergency Use Authorization for a dose-sparing intradermal route: two doses of
0.1 mL**, four weeks apart — a fifth of the volume, injected into the skin
rather than under it.

That is a large bet made quickly. This study is the check on it.

The design

A matched case-control study in 12 US jurisdictions — nine Emerging
Infections Program sites and three Epidemiology and Laboratory Capacity sites
— from 19 August 2022 to 31 March 2023, among sexually active MSM and
transgender adults aged 18–49.

Cases had a confirmed or probable diagnosis. **Controls had attended a sexual
health, HIV care or HIV PrEP clinic** in the same period without a diagnosis —
chosen so that controls resemble cases in the behaviour that matters, rather
than being the general population. **Each case was matched to up to four
controls by state or region and index date within four weeks**, and
vaccination status was verified against state registries where available
rather than taken on trust.

309 case-patients matched to 608 controls. Of the 917 in the analysis,
**206 (22.5%) fully vaccinated, 295 (32.2%) partially, 416 (45.4%)
unvaccinated.**

The answer

And the answer to the question the shortage raised

The point estimates differ, and their confidence intervals overlap heavily —
the intradermal interval runs from 22.9% to 95.0%, which is a small group
rather than a weak vaccine. **The conclusion drawn is that protection is
substantial irrespective of route**, which is what the dose-sparing decision
needed to be true.

The same holds for immunocompromise: 70.2% (95% CI −37.9% to 93.6%) among
immunocompromised participants against 87.8% among immunocompetent ones. A
lower bound below zero means the study cannot rule out no benefit **in that
subgroup**, not that none was seen.

Why the recommendation is still two doses

**Because duration of protection of 1 versus 2 doses remains unknown,
persons at increased risk for mpox exposure should receive the 2-dose
series.**

One dose at 75% is not a poor result. But the study measures protection during
its window, and how long a single dose holds is a different question that this
design cannot answer.

One finding in the demographics

**A larger share of cases than controls identified as non-Hispanic Black or
African American (27.2% vs 16.9%) or Hispanic or Latino (32.4% vs 23.4%).**
Both were adjusted for in the model — and both are, separately from the
effectiveness estimate, a statement about who was getting mpox and who was
reached by the vaccine.

Source: Centers for Disease Control and Prevention, MMWR.