An interesting update from Professor Justin Stebbing provids his own insight into the current vaccine progress. Professor Stebbing feels that there is a 75% probability that there will be enough vaccine for the entire United States population by the time of the United States election.
He argues that the rapid pace of development of a vaccine against COVID-19 is helped by various factors:
- Prior knowledge of the role of the spike protein in coronavirus pathogenesis and evidence that neutralising antibody against the spike protein is important for immunity.
- The evolution of nucleic acid vaccine technology platforms that allow creation of vaccines and prompt manufacture of thousands of doses once a genetic sequence is known.
- Development activities that can be conducted in parallel, rather than sequentially, without increasing risks for study participants.
- The non-human primates’ study and all three vaccines have shown various degrees of protection to infection and/or pathology.
This led to the United States Department of Health and Human Services launching operation Warp Speed, a partnership between government and industry with a goal of delivering 300 million doses of a safe and effective vaccine by January 2021. There are now five core candidates which hopefully will provide the results.
- Moderna using messenger RNA and is in phase 2A clinical trial, probably requiring more than a single dose.
- BioNTech using messenger RNA, which is in phase 1-2 clinical trials and may only require a single dose.
- Merck Sharp & Dohme, which uses recombinant vesicular stomatitis virus vector, which is in preclinical trials and the dosing is not known.
- Johnson and Johnson/Janssen Pharmaceuticals, which is using a replication-defective human adenovirus 26 as a vector, which is in phase 1-2A clinical trials and will only require a single dose.
- AstraZeneca and University of Oxford vaccine, which is in phase 1-2 clinical trials using a replication-defective simian adenovirus vector and will also only require a single dose.
The New England Journal of Medicine in its Moderna paper showed success in stimulating antibodies with 100% developing neutralising antibodies with lack of any significant side effects.
Professor Stebbing argues that his reasons for optimism are:
- There are three main vaccines which are going into P3 trials, which gives three solid good shots for vaccine production.
- mRMA is easy to manufacture in vast quantities and therefore costs of manufacturing are low and the ability to manufacture hundreds of millions of doses is already starting.
- Because the R0 number of the virus is low, often less than one, the FDA can allow a vaccine with only 55% efficacy, i.e. the vaccine prevents 55% of symptomatic infections.
- Interim analysis of results will come quicker because they are already having trials in the United Kingdom, Brazil and South Africa and they are looking at analyses at 50, 100 events etc.
- Neutralising antibody response. There are no published papers suggesting a documented case of re-infection. Monkeys have not been re-infected so the explanation logically is that neutralizing antibodies have been formed.
So how long will the vaccine last and provide immunity?
Professor Stebbing argues that it is known from The Lancet Spanish seroprevalence paper by King’s College, a London preprint and the Wuhan Healthcare workers in the Nature medicine paper that regularly meshed antibodies against the virus typically IgG often disappear especially in asymptomatic individuals. Whilst at present, we do not know whether they kill the virus and confer immunity despite re-infections not occurring.
However, he comments that it is known about neutralising antibodies which have not yet been measured in large seroprevalence studies or about memory T cells that there was a predominant T cell response in survivors of the 1918 Spanish flu pandemic.
A survivor of the 2003 SARS pandemic had neutralising antibodies in his blood that killed SARS-CoV-2.
In Nature this week, it is reported that 23 SARS recovered patients infected with beta coronaviruses induced multi specific and long-lasting T cell immunity to the structural protein MP and in 37 uninfected patients there also had some evidence of protective T-cells. This significance however is unclear.
Professor Stebbing goes on to summarise the data to date initially in monkeys but now in man which shows neutralising antiviral antibody responses can be achieved without any meaningful toxicity in 100% of fitter patients in a relatively small group. These neutralising antibodies appear to be responsible for preventing reinfection which is why we have never heard of true human reinfection.
The durability of immunity is still unknown. This will only be evaluated over time. The New England Journal of Medicine data showed that the individuals had a three times greater antibody level than found in convalescent plasma.
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