COVID-19 Vaccine Development: An Interview With GeoVax

The biotechnology company GeoVax Labs Inc. develops human immunotherapies and vaccines against infectious diseases and cancer. The company recently announced that it is developing vaccine candidates for the prevention/ control of SARS-CoV-2, the virus causing the COVID-19 outbreak, using its GV-MVA-VLP^TM vaccine platform.

Three vaccines have been designed and are in final steps of purification and characterization.

Technology Networks spoke with David Dodd, President and CEO of GeoVax, to learn more about the vaccine candidates, what progress has been made in clinical testing and how the company is working to accelerate vaccine development timeframes.

MC: For our readers that may be unfamiliar with GeoVax, please can you tell us about the company and its technology?

David Dodd (DD): GeoVax Labs, Inc. is a clinical-stage biotechnology company developing vaccines and immunotherapies against infectious diseases and cancer using a novel and safe viral vector platform (GV-MVA-VLP^TM).  Important attributes of GeoVax vaccines include single dose, no adjuvant, durable immunity, extensive safety and cost-effective manufacturing. GeoVax’s recombinant Modified Vaccinia Ankara (MVA) vector expresses target proteins on highly immunogenic Virus-Like Particles (VLPs) in the person being vaccinated, resulting in induction of durable immune responses while providing the safety characteristics of the replication-defective MVA vector. In lay terminology, the GeoVax platform results in vaccines that are safe and provide long-lasting protection.

Our technology and expertise have been broadly validated through development programs focused on preventive vaccines against hemorrhagic fever viruses (Ebola, Marburg, and Lassa fever), Zika virus and malaria; preventive and therapeutic vaccines against HIV; a therapeutic vaccine for chronic hepatitis B virus infections; and preventive and therapeutic vaccines for multiple solid tumor cancers. Several of our programs have received substantial federal support (>$50M to date) from the NIH and Department of Defense (DOD).  In early 2020, GeoVax initiated development of a preventive vaccine against novel coronavirus (COVID-19).

MC: GeoVax is working on using its GV-MVA-VLP^TM  vaccine platform to design and construct vaccine candidates against SARS-CoV-2. Please can you tell us more about the platform, how it works and the three vaccine candidates?

DD: GeoVax’s MVA-VLP vector vaccine platform combines the safety of a replication-defective live vector (MVA) with the immunogenicity of VLPs and the durability of immune responses elicited by vaccinia vectors. Upon vaccination, MVA-VLPs mimic a natural infection in which target proteins are displayed on the surface of the VLPs produced by the vaccine (Fig. 1 shows VLP expressing viral proteins (arrows) for our Ebola, Sudan, Marburg and Lassa fever vaccines. The VLP-displayed proteins stimulate both humoral and cellular arms of the immune system to recognize, prevent, and control target infections/diseases. The MVA vector has been optimized for retention of vaccine inserts during manufacture and we have a strong international patent portfolio that continues to expand in conjunction with our ongoing vaccine and immunotherapy developments.

GeoVax is using its GV-MVA-VLP^TM vaccine platform and expertise to develop vaccine candidates using genetic sequences from SARS-CoV-2, the virus responsible for the ongoing COVID-19 outbreak. Three vaccines have been designed and are in final steps of purification and characterization. The company is preparing to advance the vaccines into animal testing to select the lead candidate based on their safety, immunogenicity and efficacy profiles. The selected candidate will be used for manufacturing scale-up, and initial human clinical trials to determine the appropriate dose and to further confirm its safety and immunogenicity.

MC: You previously said "Our platform has a demonstrated track record of safety in humans through our HIV vaccine program" – can you expand on this statement and its relevance to developing the vaccines against COVID-19?

DD: In six Phase I and Phase II trials, including trials for both prevention and therapy of HIV, our GOVX-B11 vaccine has shown outstanding safety, tolerability and immunogenicity. GOVX-B11 is currently being tested with and without a protein boost as a preventive vaccine and is also being tested in multiple therapeutic settings in human trials toward a “functional cure”. For Ebola, Lassa, and Zika viruses, single-dose regimens of GV-MVA-VLP vaccines fully protected rodents or nonhuman primates (NHPs) against lethal viral challenges.

The GV-MVA-VLP platform has many key features and advantages over other vaccine platforms, including:

• Inherent safety of MVA
• Non-replicating in humans
• Durable humoral and cellular immunity
• Single-dose regimens provide sterile immunity
• Not hindered by prior vaccination (vector immunity)
• Self-adjuvanting
• Thermostable formulations
• Established manufacturing methods

Extensive experience with GV-MVA-VLP vectors has demonstrated their ability to raise humoral and cellular immune responses, including ADCC and neutralizing antibodies, and has provided strong precedent for safe and effective use against multiple indications. GV-MVA-VLP vaccines raise highly durable antibody and T cell responses, the most durable in the field of vectored HIV vaccines. This is consistent with the properties of the vaccinia parent of MVA, which raises highly durable responses for smallpox. The MVA-VLP platform elicits a Th1 oriented response; this may reduce the immunopathological consequences associated with vaccination and challenge with SARS and related viruses. Moreover, since our vaccine antigens are not part of the MVA structural proteins (determinants for host cell receptor biding, tropism and entry process), the safety of our vaccines are expected to be similar to that of our HIV vaccine (demonsteted excellent safety in 6 clinical trials) irrelevant to the antigen used.

MC: How is GeoVax working to accelerate the "typical" vaccine development timeframes?

DD: We have two parallel tracks for developing a safe and effective vaccine against COVID-19; one in the US and the other in China by our collaborator Bravovax located in Wuhan. The selected vaccine candidate will go through non-clinical and clinical testing in both countries. In the US we will have early discussion with the FDA on the regulatory pathway of using the vaccine under Emergency Use Authorization (EUA). We have lined up a series of collaborators and contractors to perform non-clinical studies, manufacturing, fill-finish of the product, clinical managements, QC and regulatory support. Similar activities will be conducted to manufacture and perform clinical studies in China necessary for licensure of the vaccine in that country. To accelerate the program and shorten the timelines, we will do multiple activities in parallel.

MC: Can you possibly discuss the potential logistical challenges of manufacturing and distributing a vaccine for use against a global pandemic?

DD: Of the main challenges of any vaccine designed for a wide application in healthy population is its safety. We believe our platform has shown excellent safety, the parent of our vector (MVA) has been used in the 60s as a “safer smallpox” vaccine for HIV and other immunocompromised individuals and was licensed by the FDA in 2019. Before large scale deployment in humans, we will test our vaccine candidates in relevant animal models to ensure its safety and lack of enhanced diseases as was shown with other SARS and MERS vaccines in preclinical models. Our manufacturing partners have experience in producing millions of doses necessary to stop the further spread of COVID-19. Considering numerous manufacturers who are trying to develop a COVID-19 vaccine, we anticipate licensing of multiple products to allow manufacturing of sufficient doses for global distribution. Moreover, our Chinese partner will be capable of producing sufficient vaccine for their local usage.

MC: In your opinion, what do you envision the next six months will look like in terms of developments of preventatives against the COVID-19 outbreak?

DD: In the next 6 months multiple manufacturers will be evaluating their vaccines for safety and immunogenicity in phase 1 and phase 2 clinical trials, with the expectation of obtaining a licensure in 2021 under EUA.

David Dodd, President and CEO of GeoVax was speaking with Molly Campbell, Science Writer, Technology Networks.