Authored by Brian Koffman, MDCM )retired), MSEd
Bottom Line:
CLL patients often have suboptimal COVID-19 vaccine responses and worse outcomes. GEO-CM04S1, a new type of vaccine, results in stronger T-cell immunity.
Who Performed the Research and Where Was it Presented:
Dr. Alexey Danilov from the City of Hope, Duarte, CA, led a group of researchers who presented this research as an abstract at the European Hematology Association (EHA) Annual Congress in Milan in June 2025.
Background:
It is well known that chronic lymphocytic leukemia patients have increased morbidity and mortality from COVID-19 infections. One reason for this is that they have suboptimal immune responses to the standard COVID-19 vaccines, characterized by both a less robust antibody response (humoral immunity) and a weaker T-cell response (cellular immunity). This means vaccination offers less predictable protection. To address this, GEO-CM04S1 is a next-generation COVID-19 vaccine based on a synthetic Modified Vaccinia Ankara (MVA) vector. MVA is a highly attenuated or weakened strain of the vaccinia (smallpox vaccine) virus and is now being studied as a viral vector for other vaccine development. GEO-CM04S1 is non-replicating, meaning that, although it’s a “live” vaccine, it and related vaccines have proven to be safe in immunocompromised individuals, including those who are recently post-bone marrow transplants. It is known for its safety and ability to elicit strong immune responses. Unlike the approved vaccines, it expresses both the Spike (S) and Nucleocapsid (N) proteins of SARS-CoV-2. The spike or S protein can mutate quickly, rendering vaccines less effective. The nucleocapsid (N) protein is more stable, so the vaccine should remain effective for a longer period, even if the spike protein mutates.
Methods:
A 1:1 randomized, blinded phase 2 trial was conducted in patients with CLL. They received two doses of either the Pfizer/BioNTech mRNA (with XBB.1.5 Sequence) COVID-19 vaccine or the experimental GEO-CM04S1 COVID-19 vaccine.
Results:
- A total of 31 patients enrolled (16 men and 15 women)
- Patients from both arms mounted a significant antibody increase to the spike protein. More importantly, neutralizing or killing antibodies against the original Wuhan (D614G) strain and the newer Omicron variants (BA.1 and XBB.1.5) were seen in both groups.
- As expected, only the GEO-CM04S1 arm showed N-specific antibodies post-vaccination. mRNA vaccines are only directed at the S or Spike protein of SARS-CoV-2.
- Only the GEO-CM04S1-vaccinated patients generated statistically significant S and N-specific T-cell responses.
- Both vaccines were well tolerated. There were no serious side effects (≥Grade 3). The most common Grade 1 or mild adverse events were injection site reaction (n=19), fatigue (n=12) and cough (n=10).
Conclusions and Discussions:
The Pfizer mRNA vaccine failed to elicit a significant T-cell response; therefore, the arm of the study using this vaccine has been discontinued. The hope is that while the mRNA vaccine produced stronger and more durable antibody responses, the new vaccine did produce neutralizing antibodies and, more importantly, a much more robust cellular immunity, suggesting it might be more protective in CLL patients. That remains to be proven. Several ongoing trials are studying GEO-CM0451 in CLL and other immunocompromised patients. Though it is a “live” vaccine, there have been no safety issues.
Finally, it is great to see a COVID-19 vaccine trial that focuses exclusively on CLL patients.
Resources:
Read Dr. Danilov’s EHA abstract by clicking on MVA-BASED GEO-CM04S1 VACCINE RESULTS IN IMPROVED CELLULAR IMMUNE RESPONSE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) COMPARED WITH MRNA-BASED VACCINE: INITIAL RESULTS OF A PHASE II RANDOMIZED STUDY.
