Norovirus vaccine produces mucosal immunity in phase 2b trial

News brief

An oral tablet norovirus vaccine generated mucosal immunity and reduced viral shedding in participants in a new phase 2 placebo-controlled challenge study. The results were published recently in Science Translational Medicine.

Despite being the leading cause of acute gastroenteritis (AGE) worldwide, there are currently no vaccines for norovirus (NV). In the past, phase 3 field trials have produced a lack of robust immunological correlates of protection, the authors of the study said, which is likely a problem of producing systemic, rather than targeted intestinal immunity, from the virus.

The oral tablet vaccine (VXA-G1.1-NN), built on a non-replicated adenovirus platform by Vaxart Inc, has proved to be safe and well-tolerated in previous trials. The tablet delivers NV capsid protein (VP1) to the small intestine. The current phase 2b trial included 165 individuals (18 to 49 years of age) who were randomly assigned 1:1 to receive VXA-G1.1-NN (86) or placebo (79).

30% relative reduction in norovirus

In the challenge phase of the trial, participants received an oral challenge inoculum of NV 28 days after vaccination. Among VXA-G1.1-NN recipients, 57.1% developed NV infection, compared with 81.5% in the placebo group, with a 23.6% difference (95% confidence interval (CI), 7.4% to 38.0%). Overall, there was a 30% relative reduction in AGE in those who had been given the oral vaccine.

Evidence of immunogenicity was observed in trial participants by day 28 post-vaccination. Also, stool and emesis samples showed significantly reduced viral RNA loads in the vaccinated group.

"Vaccination reduced fecal viral shedding for up to 1 week postchallenge and inhibited asymptomatic shedding (25% shedding in placebo and 13% in VXA-G1.1-NN)," the authors wrote. "Given that fecal shedding can persist for up to 60 days after infection and that the magnitude and duration of shedding are comparable between asymptomatic and symptomatic cases (41), VXA-G1.1-NN may broadly reduce environmental viral spread."

Prior COVID vaccination produces immune response against new SARS-CoV-2 strains, study finds

News brief

Stephanie Soucheray, MA

Receiving a prior COVID-19 vaccine did not prevent the immune system from producing protective responses to either Delta or Omicron virus strains, according to a new study in Nature Immunology. The findings are promising and suggest that, despite a drop in antibodies for mutated parts of the virus, vaccination offers ongoing protection from severe disease.

The study, conducted by researchers at the University of Arizona College of Medicine and their US colleagues, could help better inform booster strategies in the face of an ever-changing virus, the authors said.

The overall protective response is much, much higher than in those who were unvaccinated when infected.

"We found that even though new responses to the mutated parts of the virus are down a bit in vaccinated people who get infected, the overall protective response is much, much higher than in those who were unvaccinated when infected," said senior study author Deepta Bhattacharya, PhD, of the University of Arizona Health Sciences, in a university press release.

Neutralizing antibodies greater in vaccinated

The study compared type-specific B-cell responses in 12 unvaccinated and 37 vaccinated patients who had Delta or Omicron BA.1 SARS-CoV-2 variant infections. All vaccinated participants gotten the original vaccine targeting wild-type SARS-CoV-2 and had been infected with COVID-19 sometime from July 1, 2021, to December 1, 2021.

In general, neutralizing antibodies tested 90 days after infection were greater in participants who had been vaccinated before their variant infections than in those who had been vaccine-naive and had primary variant infections.

Delta-specific antibody production, however, was slightly reduced in those who had previously been vaccinated. But the effect was limited, as vaccinated participants still had a stronger protective antibody response to the Delta virus.

"What was really interesting is that even people whose very first exposure was to Delta or to Omicron, so there's no prior immunity at all, were making very poor responses against the mutant parts of the virus," said Bhattacharya.

Ethiopia confirms first mpox cases

News brief

Lisa Schnirring

Ethiopia has confirmed its first mpox cases, a 21-day old infant and the baby’s two parents, bringing the number of African countries reporting mpox outbreaks to 25, a top official from Africa Centre for Disease Control and Prevention (Africa CDC) said today at a weekly briefing.

Ngashi Ngongo, MD, PhD, MPH, who leads Africa CDC's mpox incident management team, said the patients are from Moyale in Oromia region, an area in far southern Ethiopia that borders Kenya, which has been battling the virus since July 2024. He said though the clade isn’t known yet, it is likely to involve 1b, which is circulating in Kenya.

The patients are in isolation for treatment, and Ethiopian health officials have established isolation centers and are conducting contact tracing.

Sierra Leone surge drives upward trend

Though cases declined a bit last week, a surge in Sierra Leone accounted for 74% of new confirmed cases and is driving an upward trend over the last 6 weeks, Ngongo said. Cases in Sierra Leone and Uganda made up 93% of the region’s confirmed cases. Efforts are underway to bolster infection control and prevention in Sierra Leone’s health facilities and community settings, with a planned deployment of 10 field epidemiologists and 200 community health workers.

Togo, which declared an outbreak earlier this month, reported 37 new cases last week, with two districts affected, he added. Malawi—another newly affected country—reported 122 new cases last week, reflecting an increasing trend, though officials are making good headway with testing coverage and contact tracing.

Ngongo said the region is experiencing a vaccine shortage, with 6.4 million doses needed between March and August. He said nearly 570,000 pledged doses from the US government and UNICEF are in limbo due to funding uncertainties. In positive developments, training to administer doses of the LC-16 vaccine donated by Japan began this week in Kinshasa in the Democratic Republic of the Congo (DRC). This week about 1.5 million doses of the LC-16 vaccine are set to arrive in the DRC, along with 100,000 doses of the Bavarian Nordic vaccine from France.