COVID & flu still nothing to sneeze at, measles headed in wrong direction, and new Moderna jab
Update issue 221
COVID and flu have receded but are not completely out yet. Infections by wastewater surveillance remain low nationally (CDC). Although positive clinical tests at 3.6% for COVID are now lower than the 4.2% in late November when the winter surge started, the current 6.7% rate for flu is still above the 2.8% when the season began in mid-November. COVID deaths at 0.7% of all causes of death for the week is a season low, but is now higher than the season low of 0.5% for flu, showing the persistence of serious COVID cases.
There were no bird flu cases reported for humans, but the 70 confirmed 4 months ago is not a hard number, because there are likely unreported cases out there.
Measles is headed for a generational high and potential loss of elimination status for the US. There are 800 confirmed cases in almost half the states as of Thursday involving 10 separate outbreaks of more than 2 cases (CDC). The largest groups are under 5 (31%) and 5-19 years old (38%). Almost all (96%) are unvaccinated, 11% have been hospitalized with the hardest hit group being 19% of those under 5, and 2 kids over 5 and an adult have died.
As of Friday, Texas has 612 cases with 597 in the west (TX DSHS).
The Michigan DHHS has reported cases linked to a large outbreak across the border in Ontario.
Vaccines
• ACIP convened last week after the then-new HHS head, Kennedy, had postponed the FDA advisors’ February public discussion of vaccine policy. In addition to other vaccines, the two-day meeting included evaluating data for a new Moderna COVID vaccine and considering whether COVID vaccines for the 2025-2026 season should be recommended for universal use as they are now or switched for at-risk populations.
For the most part, it was the usual business of science as in the past five years of Update’s coverage of ACIP.
• Moderna mRNA-1283 The data presented by Moderna were from last year, which the company has taken on the road, including a stop at the European Society of Clinical Microbiology and Infectious Diseases in Vienna days before ACIP.
The new design targets only the parts of the virus’ S(pike) protein that generate much of the protective neutralizing antibodies and T cells. These two regions at the front end of S, the N-terminal domain (NTD) and the receptor-binding domain (RBD), account for just 40% of S and thus need a shorter mRNA to encode with the potential for smaller dosing (see below). The shorter RNA is also more stable and can be refrigerated instead of frozen, increasing its distribution potential.
mRNA-1283 was developed in 2023 when the bivalent vaccines in use targeted the BA.4/5 Omicron subvariant plus the original 2020 Wuhan virus. The Phase 3 clinical trial compared bivalent mRNA-1283 for the NTD-RBDs from BA.4/5 and Wuhan to bivalent mRNA-1273 (licensed as Spikevax, the original vaccine, encoding the full-length proteins) used as a booster in over 11,000 previously vaccinated participants of whom ~75% also had prior infections.
The dose was only 10 micrograms, 20% of the 50 micrograms for the bivalent Spikevax and 10% of the 100 micrograms used in the original monovalent Spikevax for the Wuhan virus. (A technical point. Ten micrograms of bivalent 1283 would mean there were only 5 micrograms of mRNA encoding the BA.4/5 NTD-RBD protein (the other 5 for the Wuhan protein), or only 5% of the monovalent Spikevax encoding full-length S – an astounding dose reduction, but the Moderna rep did not touch on it.)
No new safety concerns occurred with no myo(peri)carditis cases or deaths. The most common local adverse effect was injection site ouch, which occurred less with mRNA-1283 due to its lower dose and jab volume. The most common systemic effects were fatigue, headache, and muscle ache.
mRNA-1283 produced 34% more neutralizing antibodies (nAb) against BA.4/5 at day 29 after vaccination than bivalent Spikevax in participants 12 and older (see Table 1A, Update’s distillation of Moderna’s data; chugalug neat or sip with the text). The results by age group revealed almost a 2-fold advantage with mRNA-1283 for people 65+ that was also durable for at least 6 months. The new 1283 formulation also boosted nAb levels (day 1 to 29) 40% higher than Spikevax (6.3-fold boost v. 4.5-fold) for people 65+ (Table 1B).
The relative vaccine efficacy (rVE) against symptomatic COVID a median of 8 months after vaccination was 9.7% better with mRNA-1283 for younger adults and 13.5% higher for adults 65+ (Table 1C). A precise reading for adolescents could not be made due to low numbers of COVID cases.
As with other COVID vaccines, the largest advantage mRNA-1283 had was in protecting people at risk for serious outcomes, with more protection for more serious conditions, from 17.5% rVE for people with at least one underlying medical condition to 38.1% rVE for severe COVID. Note that the results lacked some precision with the wide confidence intervals.
Moderna has also tested a monovalent 1283 targeting the NTD-RBD of a more recent subvariant, XBB.1.5, finding that it produced 20% more nAbs than Spikevax for full-length S. The company is planning to make a 1283 vaccine for the next subvariant and apply for authorized use in the fall. (The 1283 vaccine is also part of Moderna’s mRNA-1083 COVID-flu combo shot in development.)
Conclusion Paring the vaccine target to the domains of the S(pike) protein that generate much of the antibody and T-cell responses showed modest gains over aiming at the entire protein. At-risk populations, especially those 65 and older, benefited the most in antibody production and vaccine efficacy.
The next scheduled ACIP meeting is in late June.
• Novavax was not a scheduled topic, but it came up in a committee member’s question about its approval status. This in part made clear the difference between the new FDA leadership and Peter Marks, who was recently forced to resign (aka fired) and would have answered the question. In contrast, the political appointee overseeing the meeting would not reveal the status of the Novavax vaccine, which has been under emergency use authorization. April 1 was the FDA deadline to decide on licensing (Reuters).
However, Kennedy has claimed that vaccines using a single antigen, such as Novavax with the S protein, “have never worked” for respiratory diseases, going on to say, “… we are actually shifting our priorities to multiple antigen vaccines.” (CBS News) This imperils many US vaccines, including the S protein-encoding mRNAs and the recombinant HA protein flu vaccine.
The political appointee also interjected to question the safety and efficacy of several vaccines discussed at ACIP.
© 2025 Henry A. Choy. All rights reserved.