Blue Lake Biotechnology and its affiliate CyanVac LLC have published comprehensive Phase 1 clinical data for their intranasal COVID-19 vaccine candidate CVXGA in Science Advances, demonstrating the vaccine's potential as a safe, immunogenic, and effective single-dose intranasal immunization against SARS-CoV-2.
The open-label Phase 1 study, titled "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," enrolled 72 healthy subjects ranging from 12 to 51 years of age across four treatment groups. The study evaluated CVXGA1, a variant of CVXGA expressing the spike protein from the ancestral WA1 strain of SARS-CoV-2.
Study Design and Dosing
Group 1 received a low dose of 10^6 plaque forming units (PFU), while Groups 2, 3, and 4 received a high dose of 10^7 PFU. All participants received only one administration of CVXGA1, highlighting the vaccine's potential as a single-dose immunization.
Robust Immune Response Across Multiple Pathways
The vaccine demonstrated its ability to stimulate comprehensive immune responses across all three pillars of immunity. Participants developed consistent CD8+ T cell responses specific to the COVID S-protein four weeks after vaccination, with 92% of participants in the low dose group and 89% of participants in the high dose group mounting a response.
Mucosal immunity, a critical component for preventing respiratory infections, was also successfully induced. In the low dose CVXGA1 group, 14% of participants developed at least a three-fold increase in S-specific mucosal antibodies compared to baseline, while 31% to 41% of participants in the three high dose groups achieved this response threshold.
Vaccine Effectiveness and Safety Profile
A key finding emerged from the comparison between high-dose and low-dose recipients. Adults receiving a high dose of CVXGA1 showed a relative vaccine effectiveness of 67.8% (p=0.048) against symptomatic COVID-19 infection at a median of 7.3 months post-vaccination compared to those receiving the low dose.
The vaccine was well tolerated across all dose groups, with administration of CVXGA1 demonstrating minimal reactogenicity and no serious adverse events assessed as related to the vaccine. This safety profile supports the vaccine's potential for broad population use.
PIV5 Vector Technology
CVXGA is based on a proprietary parainfluenza virus 5 (PIV5) vector developed at the University of Georgia. The PIV5 vector utilizes a respiratory virus that is not known to cause disease in humans and has been commonly administered to dogs as part of combination distemper/kennel cough vaccines for decades, providing a foundation of safety experience.
"We believe that vaccines that stimulate all three pillars of immunity – humoral, cellular and mucosal – have the potential to be powerful public health tools that prevent symptomatic infection as well as disease transmission," said Biao He, Ph.D., founder and CEO of Blue Lake and CyanVac. "Our clinical vaccine candidates including CVXGA have regularly demonstrated an ability to generate each of these three kinds of immune responses, all while avoiding significant side effects."
Clinical Significance
Paul Spearman, MD, Professor of Infectious Diseases at Cincinnati Children's Hospital Medical Center and principal investigator of the study, emphasized the clinical potential of the approach. "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," Spearman said. "The data published on CVXGA1 show significant potential for this novel intranasal approach, particularly the relative vaccine effectiveness after 7.3 months of over 67%."
The response rates observed with CVXGA1 compare favorably against other intranasal COVID vaccines approved for use outside the U.S., according to the published data. Preclinical studies have previously demonstrated that CVXGA is immunogenic and protective and prevents transmission of SARS-CoV-2, while Phase 1 and Phase 2a clinical studies have shown robust mucosal, cellular and humoral immune responses with limited or no reactogenicity.
