SOBERANA: the Cuban way to COVID-19 vaccination
Might this RBD-tetanus toxoid conjugate be less toxic than the other options so far available?
Results of the phase III RCT evaluating the efficacy of the Cuban COVID-19 vaccine Soberana have been recently published.
We included 44,031 participants (52.0% female, 48.0% male; median age 50 years, range 19–80 years; 7.0% black, 24.0% mixed-race, 59.0% white) in a context of initial Beta VOC predominance, with this variant being partially replaced by Delta near the trial's end. Vaccine efficacy in the heterologous combination was 92.0% (95%CI 80.4–96.7) against symptomatic disease. There were no severe COVID-19 cases in the vaccine group against 6 in the placebo group. Two doses of SOBERANA-02 was 69.7% (95%CI 56.5–78.9) and 74.9% (95%CI 33.7–90.5) efficacious against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe adverse events (AE) was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient.
Soberana is a conjugate vaccine consisting of the receptor binding domain of the SARS-CoV-2 spike protein conjugated chemically to tetanus toxoid. Whether this strategy may result in reduced toxicity of the spike protein and of the vaccine as a whole awaits conformation, however in principle this product should be devoid of many of the unknowns intrinsic to the RNA, DNA/adenoviral vector and even protein subunit-based medicinals. Below the email that I recently sent to one of the principal investigators, and still awaiting response.
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Oggetto: Spike RBD
Dear Dr. Verez-Bencomo,
I read with interest and appreciation the report about the COVID-19 Soberana vaccine recently published in The Lancet.
The COVID-19 Soberana vaccine is based on a Spike RBD fragment conjugated to the tetanus toxoid. In this regard, I'd like to know whether you checked the molecule for any residual intrinsic activity of the original Spike protein.
We recently published an opinion paper documenting how most of the adverse effects induced by COVID-19 mRNA vaccines is likely due to the pharmacotoxicological properties of the Spike protein, whose production is induced in an uncontrolled manner by these products. You can find our paper here: https://www.mdpi.com/1422-0067/23/18/10881
We believe that the same is likely true for DNA/adenoviral vector vaccines and even for vaccines containing the whole Spike protein (e.g. Nuvaxovid by Novavax, which nevertheless are likely a few better since at least they contain a fixed amount of the toxin), but possibly not for vaccines like the Soberana, which includes just a fragment of the Spike protein, and in limited amounts.
However, to confirm this hypothesis it would be necessary to provide proper receptor-binding studies assessing the (in)ability of the RBD conjugate to bind relevant targets such as the ACE2 and other known molecular targets acted upon by the whole Spike protein, as well as in vivo studies in animals showing that systemic injection of the vaccine, even iv, does not induce organ and tissue damage (see e.g. https://pubmed.ncbi.nlm.nih.gov/34406358/).
Would this set of pharmacotoxicological assays confirm that the RBD conjugate is devoid of any residual effect from the whole Spike protein, then this could really represent a major achievement in the quest for a COVID-19 vaccine devoid of major adverse effects.
I would greatly appreciate your thoughts about these issues. Meanwhile, congratulations for the successful development of the Soberana vaccine.
With kind regards,