GeoVax Labs, Inc. (Nasdaq: GOVX) has reported promising clinical results for its multi-antigen SARS-CoV-2 vaccine candidate, GEO-CM04S1, demonstrating durable immune responses in both healthy volunteers and immunocompromised patients.
The clinical-stage biotechnology company presented new data at the 25th Annual World Vaccine Congress in Washington, D.C., highlighting the vaccine's performance across several Phase 1 and 2 clinical trials. The presentation, delivered by Don J. Diamond, Ph.D., showcased results from studies involving healthy adults as well as vulnerable populations including stem cell transplant recipients and patients with chronic lymphocytic leukemia (CLL).
Dual-Antigen Approach Shows Broad Immunity
GEO-CM04S1 is based on the synthetic Modified Vaccinia Ankara (MVA) vector platform and uniquely expresses both the Spike (S) and Nucleocapsid (N) antigens of SARS-CoV-2. This dual-antigen approach appears to generate broader and more durable immune responses compared to single-antigen vaccines.
In a Phase 1 trial with healthy adults, 100% of participants (34/34) produced Spike IgG antibodies, while 94% (32/34) developed Nucleocapsid IgG antibodies. Additionally, 98% (48/49) demonstrated T cell responses to either antigen following vaccination, with no serious safety concerns reported across varying dose levels.
Superior Performance in Immunocompromised Patients
Perhaps most notably, GEO-CM04S1 showed particularly strong results in immunocompromised populations—groups that have historically responded poorly to existing mRNA vaccines.
In stem cell transplant recipients, the vaccine induced antibody titers and T cell responses that exceeded those observed in healthy volunteers. More dramatically, a randomized Phase 2 trial comparing GEO-CM04S1 to the Pfizer-BioNTech (Comirnaty®) vaccine in CLL patients revealed significantly higher T cell response rates with GEO-CM04S1.
"At Day 56 of the study, 6 of 15 patients in the GEO-CM04S1 arm achieved 3-fold increases in Spike or Nucleocapsid-specific T cells versus only 2 of 14 in the Comirnaty arm," Diamond reported. The Data and Safety Monitoring Board subsequently recommended halting enrollment in the Pfizer arm due to underperformance, while continuing enrollment in the GEO-CM04S1 arm.
Effective Booster at Lower Doses
The vaccine also demonstrated strong performance as a booster in healthy volunteers previously vaccinated with mRNA or protein-based COVID-19 vaccines. In this Phase 2 booster trial, participants showed significant increases in Spike, RBD, and Nucleocapsid IgG antibody responses, as well as neutralization titers against multiple COVID-19 variants, including XBB.1.5.
Importantly, these robust responses were achieved at both higher and lower dose levels, with no meaningful differences between them—suggesting potential dose-sparing capabilities.
Potential Dual Protection Against COVID-19 and Mpox
In a separate presentation at the AAI Annual Meeting 2025, researchers highlighted GEO-CM04S1's potential to provide protection against both COVID-19 and Mpox. The presentation, titled "Immunogenicity of Synthetic MVA-based Vaccine COH04S1 Against SARS-CoV-2 in Post-HCT/CAR-T Patients and Its Cross-Protective Potential Against Mpox," revealed that sera from COH04S1-vaccinated individuals demonstrated cross-reactive immunity against Mpox virus.
These immune responses were found comparable to those in humans receiving the currently licensed smallpox/Mpox vaccine (Jynneos). Furthermore, sera from vaccinated individuals protected against lung infection in susceptible mice challenged with Mpox virus.
"These findings underscore the differentiated potential of GEO-CM04S1 to serve dual roles as both a next-generation multi-antigen COVID-19 vaccine and a cross-protective agent against Mpox," said Kelly T. McKee, Jr., M.D., Chief Medical Officer of GeoVax. "The ability to stimulate strong, broad, and durable immunity, particularly in immunocompromised individuals, represents a meaningful advancement over current vaccines."
Ongoing Clinical Development
GEO-CM04S1 is currently being evaluated in three Phase 2 clinical trials:
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As a primary vaccine for immunocompromised patients such as those undergoing stem cell transplantation or CAR-T therapy, in a randomized comparison to mRNA vaccines
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As a booster vaccine for patients with chronic lymphocytic leukemia (CLL), in a randomized comparison to an mRNA vaccine
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As a booster for healthy adults previously vaccinated with mRNA COVID-19 vaccines
"The clinical performance of GEO-CM04S1 across diverse and high-risk populations supports our mission to deliver broad and lasting protection through next-generation vaccines," said David A. Dodd, Chairman, President, and CEO of GeoVax. "Our data continues to demonstrate strong, durable immune responses in both healthy and immunocompromised populations—a critical feature of our vaccine for public health preparedness."
Market Implications
The positive clinical results come at a time when public health officials are emphasizing the need for more effective vaccines for vulnerable populations. Immunocompromised patients, including those with blood cancers and transplant recipients, remain at higher risk for severe COVID-19 outcomes despite current vaccination options.
If GEO-CM04S1 continues to demonstrate superior performance in these populations through later-stage trials, it could potentially fill an important gap in the current vaccine landscape. The added potential for cross-protection against Mpox further enhances its public health value, particularly in regions where Mpox is endemic.
GeoVax holds worldwide rights for its technologies and products, positioning the company to potentially capitalize on these developments as the vaccine advances through clinical trials.
