The first nasal COVID-19 vaccine tested in the United States has demonstrated promising results in a phase 1 clinical trial, showing a 67% reduction in infection risk compared to unvaccinated individuals. The CVXGA vaccine, developed by Georgia-based CyanVac LLC, generated both mucosal and systemic immune responses in participants, according to findings published July 4, 2025, in Science Advances.
"A single dose of this vaccine (CVXGA) was well tolerated. It generated a wide spectrum of specific immune responses including mucosal and systemic immune responses. Those who received the highest dose of the vaccine showed significantly lower rates of symptomatic COVID-19 infection," said study lead author Paul Spearman, MD, vice chair for clinical and translational research and education at Cincinnati Children's Hospital Medical Center.
Trial Design and Participants
The phase 1 trial enrolled 72 participants aged 12 to 53, with 61 completing the entire study conducted from September 2021 to May 2023. Participants were divided into four groups: one low-dose control group and three higher-dose groups including adults never infected or recently vaccinated, adults recently vaccinated with mRNA vaccines, and vaccinated teenagers.
The vaccine demonstrated a favorable safety profile, with 25% of recipients reporting runny nose and 8% experiencing nausea. No participants developed fever following vaccination.
Efficacy Results
The trial revealed striking differences in infection rates between dose groups. The low-dose control group experienced a 73.3% COVID-19 infection rate, while the three higher-dose groups showed infection rates ranging from 11.1% to 22.2%. None of the infected participants required hospitalization.
CVXGA produced a 51.9% mucosal antibody response rate across the three higher-dose groups, compared to just 21.4% in the lower-dose group. The researchers found evidence that the vaccine was absorbed in nasal tissues and generated statistically significant antibody responses as intended.
Addressing Continued COVID-19 Burden
Despite declining death rates from peak pandemic levels, COVID-19 remains a significant health concern. In the 28 days ending June 15, 2025, 663 Americans died from COVID-19, representing 67% of the 987 total deaths worldwide reported to the World Health Organization during this period. India reported 101 deaths, while Sweden reported 22 deaths.
"There is a need for improved COVID vaccines that offer more complete and durable protection," Spearman explained. "A nasal vaccine has the potential to block SARS-CoV-2 at its mucosal entry site and to reduce transmission of the virus to others."
Global Context and Future Trials
If successful in larger trials, CVXGA could join four other nasal COVID vaccines already approved internationally: two in China, one in Russia, and one in India. The nasal delivery approach could prove more effective medically and more tolerable for children and adults who fear needles.
Based on the encouraging phase 1 results, two larger clinical studies are currently underway (NCT05736835 and NCT06742281). The largest trial (NCT06742281) aims to enroll up to 10,016 participants by mid-2026, with study completion expected by mid-2027.
The researchers acknowledge that while the results suggest significant efficacy, definitive proof will require the larger trials specifically designed for this purpose. The phase 1 trial's design with low participant numbers was intended primarily to assess safety and initial immune responses rather than provide conclusive efficacy data.
