Intranasal COVID-19 Vaccine Found Safe and Immunogenic in Open Label Phase 1 Clinical Trial

A first-in-human trial of the investigational intranasal COVID-19 vaccine CVXGA1 found that a single dose was well tolerated and generated mucosal, humoral, and cellular immune responses in teens and adults, according to results published in Science Advances.1

Paul Spearman, MD

Courtesy of Cincinnati Children's

Developed by Blue Lake Biotechnology and CyanVac, the vaccine uses a parainfluenza virus 5 (PIV5) vector encoding the ancestral SARS-CoV-2 spike (S) protein. The nasal spray is being evaluated as a potential tool to curb transmission and symptomatic infection.2

The open-label phase 1 study enrolled 72 healthy participants aged 12 to 53 years who were categorized into 4 groups: 1. COVID-19 vaccine-naive adults; 2. Adults exposed to SARS-CoV-2 more than 6 months earlier; 3. Adults exposed to SARS-CoV-2 or received an mRNA vaccine at least 6 months before receiving study drug; and 4. Adolescents aged 12 to 17 years exposed to SARS-CoV-2 or received an mRNA vaccine at least 6 months before receiving study drug.1

The mean age of groups 1, 2, and 3 was approximately 35.5 years; the adolescents in group 4 had a mean age of 14 years, according to the study.

Participants in group 1 received a low dose (10⁶ plaque forming units [PFU]) and participants in groups 2-4 a high dose (10⁷ PFU) of CVXGA1. A total of 61 participants completed the trial, conducted between September 2021 and May 2023.1

Four weeks following vaccination, CD8+ T cell responses specific to the S-protein were observed in 92% of participants in the low dose group and 89% in the high dose groups.1 Between 31% and 41% of recipients in the high dose groups developed at least a 3-fold increase in mucosal S-specific antibodies from baseline. The rate in the low dose group was 14%, the researchers reported. Response rates in both groups compared "favorably" with data reported for intranasal COVID-19 vaccines approved outside the US, the investigators wrote. A comparison of high- vs low-dose recipients demonstrated a relative vaccine effectiveness of 67.8% (P =.048) against symptomatic COVID-19 at a median of 7.3 months following vaccination.1

“COVID-19 continues to cause disease and drive hospitalizations across the globe. COVID vaccines that cause fewer side effects, provide long-lasting protection, and diminish transmission of the virus would be highly desirable,” Paul Spearman, MD, principal investigator of the study and professor at Cincinnati Children’s Hospital Medical Center, said in a statement.2 “The data published on CVXGA1 show significant potential for this novel intranasal approach, particularly the relative vaccine effectiveness after 7.3 months of [more than] 67%.”2

SARS-CoV-2 initially infects and replicates in the upper respiratory tract, which plays a key role in the pathogenesis of COVID-19. Preventing viral replication at this site before it progresses to the lungs is a desirable goal for prophylactic vaccines—one that intranasal immunization may help achieve, study authors wrote.1 They also suggest that among other reasons for reduced efficacy of current vaccines over time is that intramuscular delivery precludes sufficient blockage of upper respiratory tract transmission. They note that the nasal spray delivery approach has precedent, pointing to the first approved cold-adapted live attenuated influenza vaccine (LAIV; AstraZeneca) in the US, which is delivered intranasally and targets the same mucosal surfaces.1

CVXGA1 demonstrated good safety and tolerability, with only mild adverse effects (AEs) reported in the study. Approximately 25% of participants reported a runny nose and 8% reported nausea. Spearmen et al made no reports of fever and no serious AEs were deemed related to the vaccine.1

Phase 2a studies are underway, according to the company statement.2

The threat from COVID-19 persists despite scant news coverage in recent months, and the need for improved vaccines continues. In 2024, the mortality rate from COVID-19 infection was 1.7% higher than from influenza in the US.3 Moreover, from May 18 to June 15, 2025, COVID-19 accounted for 663 deaths in the US, representing 67% of the 987 deaths worldwide reported to the World Health Organization during that period.4 Despite the waning visibility of the pandemic, SARS-CoV-2 remains a significant public health burden.

References

1. Spearman P, Jin H, Xizo P, et al. Safety and immunogenicity of intranasal parainfluenza virus type 5 (PIV5)–vectored COVID-19 vaccine in adults and teens in an open-label phase 1 trial. Sci Advance. 2025;11(27). doi:10.1126/sciadv.adw0896

2. Blue Lake and CyanVac publish full data from open label phase 1 clincal study of COVID-19 vaccine candidate. News release. July 7, 2025. Accessed July 7, 2025. https://www.bluelakebiotechnology.com/news/blue-lake-and-cyanvac-publish-full-data-from-open-label-phase-1-clinical-study-of-covid-19-vaccine-candidate

3. Griffin I, King J, Lyons BC, et al Estimates of SARS-CoV-2 hospitalization and fatality rates in the prevaccination period, United States. Emerg. Infect. Dis. 30, 1144–1153 (2024).

4. WHO COVID-19 dashboard. World Health Organization. Last updated June 15, 2025. Accessed July 7, 2025. https://data.who.int/dashboards/covid19/deaths