Animal Models Show Full Protection Against Omicron Variant Despite Absence of Neutralizing Antibodies, Highlighting Critical Importance of T-cell Immunity for Next-generation COVID-19 Vaccines

ATLANTA, GA - December 18, 2025 (NEWMEDIAWIRE) - GeoVax Labs, Inc. (Nasdaq: GOVX), a clinical-stage biotechnology company developing multi-antigen vaccines and immunotherapies against infectious diseases and cancer, today announced the publication of a peer-reviewed article in Frontiers in Immunology titled: “Multi-antigen MVA-vectored SARS-CoV-2 vaccine, GEO-CM04S1, induces cross-protective immune responses to ancestral and Omicron variants.”

The study provides definitive preclinical evidence that GeoVax’s multi-antigen COVID-19 vaccine candidate, GEO-CM04S1, delivers full cross-variant protection, driven predominantly by robust T-cell responses, even in the absence of neutralizing antibodies.

The findings reinforce the design philosophy behind GeoVax’s MVA-based, multi-antigen platform and provide mechanistic insight that is increasingly relevant for immunocompromised individuals, who often fail to respond optimally to the first-generation COVID-19 vaccines.

Study Highlights: Multi-Antigen Breadth and T-Cell Immunity Drive Protection

The study evaluated GEO-CM04S1 in the K18-hACE2 lethal mouse model, comparing immune responses and efficacy to experimental MVA-vectored vaccine constructs expressing spike alone (S) or nucleocapsid alone (N). Key findings include:

• Full protection against both ancestral B.1 and Omicron XBB.1.5: Only GEO-CM04S1 (S+N) maintained 100% survival, preventing weight loss, severe lung inflammation, and virus replication in both upper and lower airways.
• Protection against XBB.1.5 occurred despite no detectable neutralizing antibodies: Neutralization assays showed zero detectable neutralizing activity against XBB.1.5 in any group - yet GEO-CM04S1-vaccinated animals were fully protected. This indicates immunity was not antibody-dependent.
• CD4+ T cells were identified as the critical effector of protection: Antibody-mediated depletion studies showed:
  • Loss of CD4+ T cells eliminated vaccine protection, leading to high viral loads and severe lung pathology.
  • Depletion of CD8+ T cells or B cells had minimal impact on vaccine efficacy.
  • These results confirm T cell responses as the critical component of vaccine-induced immune responses capable of providing cross-variant protection.
• Multi-antigen design (Spike + Nucleocapsid) outperformed spike-only vaccines: GEO-CM04S1 delivered broader and more durable immunity than spike-only MVA vaccines - especially when spike was mismatched to circulating variants.

“This publication provides significant evidence supporting the unique value of a multi-antigen designed to induce high levels of T-cell responses and validates the core design principles that differentiate our vaccine from first-generation, spike-only approaches,” said Mark Newman, PhD, Chief Scientific Officer of GeoVax.

Dr. Newman added: “These findings  support the belief that the GEO-CM04S1 vaccine could be a highly relevant product for use in immunocompromised patients,  because of the ability to protect through strong, multi-antigen T-cell immunity.”

“This peer-reviewed study provides a compelling scientific foundation for the ongoing clinical advancement of GEO-CM04S1,” stated David Dodd, Chairman & CEO of GeoVax. “As SARS-CoV-2 continues to evolve, it is increasingly clear that next-generation vaccines must move beyond spike-only strategies. GEO-CM04S1 demonstrates the breadth, durability, and variant-proof characteristics that global public-health leaders have been calling for.”

Dodd continued: “More than 40 million immunocompromised individuals in the U.S. alone remain underserved by existing vaccines. The results published in Frontiers in Immunology strengthen the rationale behind our multiple ongoing Phase 2 studies in immunocompromised patient populations.”

About GEO-CM04S1

GEO-CM04S1 is an MVA-vectored vaccine encoding both the Spike (S) and Nucleocapsid (N) proteins from SARS-CoV-2, designed to induce:

• Strong CD4+ and CD8+ T-cell responses
• Durable immunity supported by conserved N-protein recognition
• Multi-antigen breadth that mitigates loss of protection as the virus mutates

GEO-CM04S1 is currently being evaluated in multiple Phase 2 clinical trials in immunocompromised patients, including individuals with hematologic cancers and chronic lymphocytic leukemia.

About GeoVax

GeoVax Labs, Inc. is a clinical-stage biotechnology company developing novel vaccines against infectious diseases and therapies for solid tumor cancers. The Company’s lead clinical program is GEO-CM04S1, a next-generation COVID-19 vaccine currently in three Phase 2 clinical trials, being evaluated as (1) a primary vaccine for immunocompromised patients such as those suffering from hematologic cancers and other patient populations for whom the current authorized COVID-19 vaccines are insufficient, (2) a booster vaccine in patients with chronic lymphocytic leukemia (CLL) and (3) a more robust, durable COVID-19 booster among healthy patients who previously received the mRNA vaccines. In oncology the lead clinical program is evaluating a novel oncolytic solid tumor gene-directed therapy, Gedeptin®, having recently completed a multicenter Phase 1/2 clinical trial for advanced head and neck cancers. GeoVax is also developing a vaccine targeting Mpox and smallpox and, based on recent EMA regulatory guidance, anticipates progressing directly to a Phase 3 clinical evaluation, omitting Phase 1 and Phase 2 trials. GeoVax has a strong IP portfolio in support of its technologies and product candidates, holding worldwide rights for its technologies and products. For more information about the current status of our clinical trials and other updates, visit our website: www.geovax.com.

Forward-Looking Statements

This release contains forward-looking statements regarding GeoVax’s business plans. The words “believe,” “look forward to,” “may,” “estimate,” “continue,” “anticipate,” “intend,” “should,” “plan,” “could,” “target,” “potential,” “is likely,” “will,” “expect” and similar expressions, as they relate to us, are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. Actual results may differ materially from those included in these statements due to a variety of factors, including whether: GeoVax is able to obtain acceptable results from ongoing or future clinical trials of its investigational products, GeoVax’s immuno-oncology products and preventative vaccines can provoke the desired responses, and those products or vaccines can be used effectively, GeoVax’s viral vector technology adequately amplifies immune responses to cancer antigens, GeoVax can develop and manufacture its immuno-oncology products and preventative vaccines with the desired characteristics in a timely manner, GeoVax’s immuno-oncology products and preventative vaccines will be safe for human use, GeoVax’s vaccines will effectively prevent targeted infections in humans, GeoVax’s immuno-oncology products and preventative vaccines will receive regulatory approvals necessary to be licensed and marketed, GeoVax raises required capital to complete development, there is development of competitive products that may be more effective or easier to use than GeoVax’s products, GeoVax will be able to enter into favorable manufacturing and distribution agreements, and other factors, over which GeoVax has no control.

Further information on our risk factors is contained in our periodic reports on Form 10-Q and Form 10-K that we have filed and will file with the SEC. Any forward-looking statement made by us herein speaks only as of the date on which it is made. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law.

Company Contact:
info@geovax.com
678-384-7220

Media Contact:
Jessica Starman
media@geovax.com 

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