Does BANCOVID meet the standards for human clinical trials?
According to the preprint, Globe did use only 6 mice (3 male + 3 females). It is expected that a total of 100 mice should have been injected for BANCOVID. But Globe used only 30 mice. Therefore, Globe did not categorically follow the WHO guidelines and the data generated from animal experiments come into serious questions. The approach that is scientifically acceptable in the field is that each observation (research experiment) whether performed in vitro or in vivo must be repeated independently in a similar condition using same number of animals. The data must be reproduced for any conclusion that authors inclined to provide. Unfortunately, Globe's pre-print manuscript has no documentation in this aspect and data cannot be reliable.
In addition, because of the concerns of the experts during high speed COVID-19 vaccine development, many vaccine developers including Moderna/NIH, BioNTech/Pfizer, Janssen Pharmaceuticals and Oxford/AstraZeneca have published their non-clinical studies in top-ranked journals to show the quality of their data while Globe Biotech has not published their studies yet in any peer reviewed journal.
Does Globe's vaccine candidate induce optimal immune response in the preclinical studies?
Vaccine-induced immune responses and its relevance in protection of animals are other critical elements to evaluate during preclinical studies. Globe Biotech should keep in mind that vaccine efficacy at preclinical stage remains the gold-standard in order to go to the next level, Phase 1 clinical trial. The claimed preclinical data of Globe Biotech are very poor in the sense of data quality, immunogenicity as well as efficacy.
1# Candidate vaccine of Globe Biotech induces antibodies which they have claimed to be important due to D614G mutation in CVOID-19, which actually has not been further characterized by testing against any pathogenic strains of SARS-CoV-2 with D614G mutation. Most importantly, the candidate has not been tested against any available SARS-CoV-2 strains isolated from infected patients. Therefore, the novelty what they claimed is highly questionable.
2# The response which Globe has claimed Th1 balanced is also based on vague antibody classes; this idea is already outdated and not acceptable in the field. On top of that, their data does not show significant change by the ratio of antibody class switch (0.8 is negligible).
3# Neutralization assay was done using recombinant pseudo virus, which people often do. But such a preclinical study was done without in vivo challenge using SARS-CoV-2 strain isolated from patients. It is premature to make a solid claim that antibody responses were enough to prevent SARS-CoV-2 infection.
4# T cell data in their pre-print is simply not showing any response. Globe Biotech just has claimed it as Th1 response. This data need to be checked by expert Immunologists before sending for publication. Data quality, flow cytometry gating on specific population and the cytokines that they measured, none of those is done in the way what a standard immunology lab does in this present time.
Most importantly, Globe Biotech has exaggerated highlighting the specificity of their vaccine targeting the D614G mutation. In fact, D614G mutation is outside the receptor binding domain (RBD) and hence doesn't need to be focused in developing a COVID-19 vaccine. Globe Biotech must refrain from such false scientific statements. Therefore, it is truly important not to mislead people and scientists until Globe makes solid data from their preclinical studies with their vaccine candidate.
Is enlisting in the WHO website as a candidate vaccine means international approval or recognition?
Answer is NO. WHO has repeatedly mentioned a disclaimer in every page of the enlisting document : Inclusion of any particular product or entity in any of these landscape documents does not constitute, and shall not be deemed or construed as, any approval or endorsement by WHO of such product or entity (or any of its businesses or activities). While WHO takes reasonable steps to verify the accuracy of the information presented in these landscape documents (i.e only a few info- vaccine type, company name, county of origin, dose and stage of development) WHO does not make any (and hereby disclaims all) representations and warranties regarding the accuracy, completeness, fitness for a particular purpose (including any of the aforementioned purposes), quality, safety, efficacy, merchantability and/or non-infringement of any information provided in these landscape documents and/or of any of the products referenced therein."
COVID-19 vaccine development is monitored internationally. If something goes wrong in human trials, the hard-earned reputation of Bangladeshi pharmaceutical companies exporting over USD 130 million worth per year of generic drug business could be at stake. Therefore, the regulatory authority of Bangladesh must seek expert opinion from reputed international regulatory agencies for ensuring the quality and safety of the BANCOVID-19 before giving its approval for human clinical trials.
Globe Biotech Limited is developing the COVID-19 vaccine candidate for human use and obviously not for mice. Globe cannot start human trials just from some basic in vitro and mice studies due to poor quality of the data. It is also unacceptable and could be dangerous that Globe Biotech attracts public by the media using false scientific statements for instance mentioning the Th1 response which is not even induced by their vaccine candidate. We should realize that the preprint manuscript of Globe Biotech is not just an academic manuscript but it involves human health and safety if they want to pursue Phase I clinical trial.
Therefore, Globe Biotech must follow the international guidelines for vaccine development including those of the WHO, ICH, EMA and FDA. Bangladesh Government regulatory authority namely the Directorate General of Drug Administration (DGDA) must assure that Globe Biotech Limited strictly meets those international guidelines to be able to start human trials to safeguard the people of our country. Ensuring the health and safety of the people is the crucial responsibility of the government of any country and we hope that the Bangladesh Government will set international standards to be proud of.
Dr Rezaul Karim is an immunologist and former project lead at
WHO-Utrecht Centre of Excellence for Affordable Biotherapeutics, The Netherlands.
Dr Jubayer Rahman is immunologist working at the National Institutes of Health, USA.
Dr M Shamsul Alam, Immunologist working at the National Institutes of Health, USA.
Dr Mohammad Sorowar Hossain, Former Senior Manager (R&D), Biotech Division, Incepta Pharmaceutical Ltd; Associate Professor, Independent University, Bangladesh; Executive Director, Biomedical Research Foundation, Bangladesh.
Professor Dr Md Anwar Hossain, Vice-Chancellor, Jessore University of Science and Technology, Researcher on vaccine development.