During the 2022 Omicron wave, Novavax’s protein-based COVID shot had an estimated 50% vaccine effectiveness (VE) against symptomatic Infection in fully vaccinated people and a VE of 31% in those who were partially vaccinated, an Italian study has determined.

The vaccine was slightly less effective in preventing any notified infection to the country’s COVID-19 surveillance system, at 23% for partially vaccinated people and 31% for fully vaccinated people, reported Alberto Mateo-Urdiales, PhD, of the Istituto Superiore di Sanità in Rome, and colleagues in JAMA Network Open.

Protection against any notified infection waned over time, decreasing from 41% in the first month after completion of the two-dose primary series to 28% at 3 to 4 months afterward. However, the researchers noted, effectiveness against symptomatic infection remained stable, ranging from 48% to 55%.

As expected in the face of the more immune-evasive Omicron variant, the data are a sharp contrast to the pivotal trial data, which showed a 95% efficacy against infection caused by the original Wuhan strain of SARS-CoV-2 and 85% against the B.1.1.7 (Alpha) variant; that data provided support for the FDA’s emergency use authorization of the non-mRNA vaccine.

These are the first independently gathered effectiveness data on the protein-based vaccine, according to Mateo-Urdiales and coauthors.

“Although several observational studies have used clinical data to estimate effectiveness of mRNA vaccines against infection and symptomatic COVID-19, to date there are no studies that we know of estimating the effectiveness of the protein recombinant vaccine NVX-CoV2373,” the investigators said.

On Tuesday, Novavax’s updated vaccine was authorized by the FDA, a monovalent formulation targeting XBB.1.5, as requested by the FDA and its advisors. While that strain is now causing just 1% of national infections, according to the CDC’s variant tracker, the updated shots from Novavax, Moderna, and Pfizer/BioNTech have been shown to neutralize other currently circulating variants.

Novavax has said its vaccine can neutralize EG.5 (Eris) — currently the most-common variant in the U.S., causing 29.4% of infections — as well as XBB.1.16.6, XBB.1.5, XBB.1.16, and XBB.2.3. The company hasn’t shared data about whether the vaccine works against FL.1.5.1 (Fornax), which is currently causing 13.7% of infections, nor against BA.2.86 (Pirola). A newly recognized variant of concern, Pirola has at least 30 mutations in the spike protein, prompting some concerns about enhanced immune evasiveness. Though BA.2.86 has been detected in the U.S., it hasn’t registered on CDC’s tracker.

The retrospective cohort study from Mateo-Urdiales and colleagues comprised 20,903 adults in the Italian National Vaccination Registry who received the Novavax vaccine from February to September 2022. Their mean age was 52 years; most (98.5%) had no risk factors associated with severe COVID-19.

The primary outcomes were SARS-CoV-2 infection confirmed by PCR or antigen testing, and symptomatic COVID-19. These outcomes were analyzed during the partial Vaccination Period (day 15 after the first dose until 14 days before the second dose) and the full vaccination period (15 days and onward after the second dose). Most individuals (89.5%) started their primary series before or during March. The median follow-up was 156 days.

Investigators used the first 10 days after first vaccination as the reference period. During this period, rates of SARS-CoV-2 infection were highest (237.8 per 100,000 person-days). In the period of partial vaccination, rates were lower (196.2 per 100,000 person-days; adjusted VE 23%). Rates were lowest in the period 15 days after the second vaccination (147.3 per 100,000 person-days; adjusted VE 31%).

Symptomatic infections followed the same pattern: 91.5 infections per 100,000 person-days in the reference period, 70.6 per 100,000 person days in the partial vaccination period (VE 31%), and 45.8 per 100,000 person-years in the full vaccination period (VE 50%).

Mateo-Urdiales’s team also looked at hospitalizations, but the rates were too low for statistical analysis, with one hospitalization in the reference period, seven in the partial vaccination period, and 18 in the full vaccination period.

The waning protection against all infection was similar to that seen with mRNA vaccines, the researchers noted, but the persistent protection against symptomatic infection appeared to be a plus for the protein-based formulation.

“In concordance with previous studies focused on mRNA effectiveness, we observed a decrease in the protection conferred by vaccination against SARS-CoV-2 infection through time,” they wrote. “However, observational studies have also reported a decrease in protection against symptomatic COVID-19 after completion of the primary cycle with mRNA vaccines, which was evident within 4 months after completion of the cycle, whereas we did not find any evidence of waning against symptomatic COVID-19.”

“It is unclear whether such discrepancy in the findings is due to a better sustained protection of NVX-CoV2373 compared with mRNA vaccines or whether it is the consequence of methodological and/or symptoms reporting heterogeneity,” they added.