Latest Data on SARS-CoV-2 Vaccines: COVID-19 Science News

8 min readJul 26, 2020

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Preface

A few days ago, the EU summit in Brussels concluded and agreed on a budget for science which totals €1.8 trillion over 7 years, which in practice will likely result in a reduction in budget for bodies such as the European Research Council (ERC) which funds basic science research. [1]

Author’s note: For those unfamiliar with the terminology, basic or fundamental science refers to scientific research which is done without any direct application in mind. It is critical to understand that basic science arguably contributes as much (or perhaps more) to technology and other applications as applied research does, but it does so often over a longer time-frame. A few examples of technologies that are rooted in basic science are MRIs (based on NMR), gene therapy (based on fundamental genetics), LCD displays (based on liquid crystals, initially simply a scientific curiosity) and GPS location (relativistic corrections are needed).

Overall, this is both a decrease in funding compared to a previous proposal and a lower amount than was hoped for from the community. The events of the past few months globally have demonstrated the utmost importance of funding science. Applied science clearly is extremely important, seen in the clinical trials being run, the testing of infectivity and of course vaccine development. However, fundamental science has played an enormous role as well. Efforts such as identifying mutations in the virus and even the tests which are run around the world are based on science (phage display & PCR) that was initially discovered simply for the sake of it and not with applications in mind.

It would be ideal if public perception will shift when all this is over and that everyone will recognise the need for funding both applied and basic science.

Essentially, the message given by the political leadership to scientists sounds like the following:

“Hey, can you fix this problem that we have because we did not listen to your advice and cautions? Yeah can you get that stuff we need about 5 times faster than normal? Thanks. Oh and by the way, we will be giving you less funding, have a great day!”

Vaccine Results

Pfizer has released additional data for their first (of 4) vaccine candidate, BNT162b1, analysing T-cell responses for their patients. [2]

The reason T-cell analysis is a big deal is because it can give a better picture of how a given vaccine may prime patients for long-term immunity.

In addition to a robust dose-dependent neutralising antibody response which was reported previously (see corresponding blog post [3]), the new research shows that almost all patients in all dose groups (1 to 50 μg) develop CD4+(34/36 patients) and CD8+ (29/36 patients) T-cells which were not present pre-vaccination. [4]

Some of the T-cell data reported by the Pfizer-BioNTech collaboration for their candidate vaccine BNT162b1. a. T-cell response for patients. b. Example of spots for a patient from the 10 μg dose group. c. Specificity of T-cell responses RBD of SARS-CoV-2 vs. CEFT (CMV, EBV, influenza virus, tetanus toxoid HLA class II epitopes). Credit: source [2]

To simplify (way too much), a vaccine which shows a strong and specific T-cell response containing both CD4+ and CD8+ is likely to impart long term immunity (longer than the amount of time antibodies remain in the bloodstream; the exact number will depend on the disease) and an effective immune response in the case of infection post-vaccination. [5]

Author’s note: immunology is A LOT more complicated than that and the author does not presume to understand even a small fraction of it. Some resources for learning more about immunology and T-cells are included at the end of this note. [6-8]

The data for Moderna’s mRNA vaccine candidate mRNA-1273 has finally been released, months after the initial press release. [9]

The patients took roughly 40 days after a second shot of the vaccine (which causes more side-effects, as expected) to raise levels of neutralising antibodies similar to those seen in recovered patients. The team only sees CD4+ T-cell responses and not CD8+; the implications of this are as of yet unknown. [10]

Overall, the antibody response seems acceptable, as are side-effects and T-cell responses look quite different to the Pfizer/BioNTech data, which could be good or bad. Considering this study did not include any patients that would be at high risk for COVID-19 (age > 55 years, comorbidities), as a phase I study should, it is understandable that there is some skepticism surrounding the vaccine candidate. [11]

CanSino has released the data for their phase I clinical trial of their adenovirus vaccine candidate. This is the same vaccine candidate that has allegedly been approved for use in the Chinese military. [3,12]

T-cell response of patients to the CanSino adenovirus vaccine. Left data are at day 0 pre vaccination and data on the right are 28 days post vaccination. Note that the y axis is in 10⁵ and not 10⁶ cells which is what is typical. Credit: source [12].

This trial included some older patients (>55 years old), which is notable. Side-effects were typical, with no patients experiencing any that were classified as severe. Older patients and patients with pre-existing antibodies against the adenovirus 5 (Ad5) vector raised 2–3 times lower levels of antibodies than patients who did not. T cell testing also does not look great (see above figure and note that it is per 100,000 cells and not per 1 million as is normal cf. Pfizer data above). [13]

Unfortunately, the outlook for the CanSino vaccine is not fantastic, given the inability to administer booster shots and the low antibody and T-cell responses especially for older patients and patients with anti-Ad5 antibodies.

The Oxford/AstraZeneca collaboration has released the data for their combined phase I/II trials for their vaccine candidate ChAdOx1. [14]

Compared to the other vaccine efforts this one has received a much larger amount of media attention, however based on the results it is difficult to understand why.

An initial observation comes at the patient population used. There are no participants aged over 45 years old, there are only 9 % non-white participants and the median BMI is 24 (in the UK median BMI is ~27.5 [15]). This patient population is completely appropriate for a phase I trial, however, it is hard to justify as a phase II trial, due to the fact that it does represent the population as a whole nor does it examine groups that may be at increased risk.

The study is considered phase II as it will examine infection rates between groups that took ChAdOx1 or a meningitis vaccine as a placebo, however this data has not been made available yet. We very eagerly await these results.

In terms of side-effects, there were no severe events and the profiles were similar to those reported for other vaccines. Compared to the meningitis control there were more side-effects (soreness, headache etc.) and treatment with paracetamol led to a reduction of these effects. The second dose did not appear to induce stronger side-effects which is a bit curious. [16]

Comparison of the neutralising antibody data between the ChAdOx1 vaccine candidate (top) from Oxford/AstraZeneca and the BNT162b1 vaccine from Pfizer/BioNTech (bottom). Credit: sources [4] and [14].

In terms of antibodies, patients raised neutralising antibodies, at levels comparable to or slightly lower than recovered patients. When compared to the data released by Pfizer/BioNTech, it can be seen that the antibody response is much weaker. Notably in the Oxford/AZ study some of the patients started off with antibodies already before vaccination, meaning that they recruited some patients that had already been infected at some point in time.

T-cell spotting data from patients inoculated with ChAdOx1. Credit: source [14].

A T-cell response was mounted by patients which persisted for 56 days, it is nice to see some data on the time dependence of this response. However, there is no data on the types of T-cells (CD4+ and CD8+) so a comparison with the other vaccine candidates discussed above is difficult.

Overall, though the data look less favourable than for other efforts, it is not yet known what levels of antibodies and cellular responses are required to provide an effective vaccine. Therefore, it is possible that all of the above vaccine candidates will end up being effective or that indeed none at all will.

Vaccine Pricing

Onto vaccine pricing, which many people and journalists online have been up in arms about. Astrazeneca and Oxford have announced that ChAdOx1 will be distributed at no profit as most funding is being supplied by governments. They aim to deliver 400 million doses to the EU, 300 million to the US and 1 billion doses to low and middle income countries, should the vaccine prove effective. For developing countries a cost of $2.50 per dose has been rumoured. [17,18]

J&J has also stated that their vaccines will not be sold at a profit during the pandemic in case of successful trials. Moderna and Merck have been unclear in their statements on whether they plan to make a profit. [19–21]

Pfizer has said they plan to sell for profit and they have announced a price of $19.50 per dose, with 1 billion doses planned. Of all companies mentioned, Pfizer is the only company that has not received any government funding for the development of their vaccine candidates. [22]

All of the above vaccine candidates have already begun production before knowing whether they will be successful, meaning that in case of failure they will simply take the hit.

It has been estimated that vaccine candidates which succeed in phase I have a 1/3 chance to make it to approval. However, this is for regular development times and for technologies which are known. The former is not the case for any programs and the latter is only true for some programs, the mRNA programs do not fall under this category for example. Overall, it is practically certain that we will eventually have some vaccine. [23,24]

References

Latest Data on SARS-CoV-2 Vaccines: COVID-19 Science News

Written by Michael Bogdos