Industry Updates Volume 11

Global Covid Pandemic - Booster shots against the Delta variant

• The pandemic has entered a significant new phase with the approval of 3rd, 'booster', vaccine shots in Israel and the United States, and similar approvals are expected shortly in the UK, Canada, Germany, France and elsewhere. This has been criticized by the WHO as worsening the vaccine shortage for poorer countries.
• The first such decision, in Israel, was due to the inability of double vaccination by the Pfizer- BioNTech mRNA vaccine to prevent Covid infection by the Delta variant. Despite having had the fastest full vaccination program in the world, the infection rate since Delta is as high as the pre-vaccination peak; and is one of the highest new Covid infection rates in the world. The following graph from the Israeli Ministry of Health illustrates how 2 shots of the Pfizer vaccine is providing very little protection against infection from the Delta variant.
• The ineffectiveness of two Pfizer vaccine shots to prevent new infection has been attributed to the fast waning immunity of mRNA vaccines. A less discussed, but possibly more significant issue, is the growing gap between any vaccine based only on the Spike protein of the original Chinese virus, compared with the latest mutations of the whole virus as seen in the Delta, and some other variants e.g. Lambda. Albert Bourla, CEO of Pfizer, said on Fox News this week that he expected Covid variants to emerge which would completely evade current Covid vaccines.
• Israel has now provided 1.5 million Pfizer vaccine booster shots (3rd dose) in three weeks, covering 60% of the population above 60, and has lowered the age for a booster to 30 for the general public, and no age limit for special groups e.g. teachers, healthcare workers etc.
• On a positive note, the Israeli data appears to show that the rate of severe Covid illness e.g. hospitalisation or death, is 80%-90% lower among fully vaccinated than unvaccinated parties (unless the unvaccinated party had recovered from Covid - see below). Similar data has been seen in Los Angeles County. As of yesterday Israel had 361 seriously ill patients who had been fully vaccinated, and 330 who were unvaccinated; 5.5m eligible people are fully vaccinated. Whereas 1.1m eligible people are unvaccinated. This translates to about an 80% protection rate from serious illness for vaccinated individuals.​

PROTECTION BY VACCINES - is anything better than mRNA?

• A substantial amount of research suggests that a second or third shot of a DIFFERENT type of vaccine appears to provide greater protection than more shots of the same. This finding however appears to have been ignored in both the Israeli and US booster shot decisions.
• Oxford University has issued a research report which indicates, based on antibodies, that the immunity generated by the AstraZeneca 'Oxford' Adenovirus vaccine, while initially much lower than mRNA vaccines, declines more slowly, such that they might provide equal antibodies at about 5 months from vaccination.
• There are major unknowns as to what will create longer term immunity against Covid e.g. the reaction of T-cells and memory B cells, as compared with short term antibody production.
• Questions have been asked about the relative importance of the different types of antigens generated e.g. IgG antigens in the serum, as opposed to  IgA antibodies in the nasal mucus.
• More broadly there is a scientific question whether a whole virion (e.g. Whole Inactivated Virus) vaccine will provide greater protection against mutations over time as there are significantly more epitopes (unique parts of the virus) for the immune system to recognize as compared to  the small number of epitopes on the Spike protein, which have undergone the greatest number of mutations (e.g. Delta).. 
• Allied to this is the question as to the role of the Nucleocapsid ('N-protein') in providing long term immunity, including against further variants, and even against other Coronaviruses. Data seems to support a critical role for this protein in generating a robust long lasting immune response. A WIV vaccine contains both the spike and the nucleocapsid, as well as many other antigens, which may be critical to the generation of a long term robust immune response. 
• Data from countries which have predominantly used WIV vaccines supports the hypothesis that the whole virion is more protective against Delta than vaccines based only on Wuhan Spike protein. 
• The graph shown below compares 4 countries with large-scale use of WIV vaccines (Chile, Brazil, India, and Indonesia) with 3 countries relying mostly on mRNA (USA, Israel, and the UK).
• The next section examines whether natural infection with the whole Covid virion is substantially protective against Delta.

Does Natural Infection provide better protection against Delta COVID than Vaccination?

• Vaccines try to protect against infection by generating an immune response, as occurs after a natural infection: this can then prevent subsequent reinfection by the same disease. The latest technologies aim to create vaccines engineered to generate un-naturally high levels of short term antibodies. The critical question regarding the “new” vaccines is not their short term impact on disease but rather the protection afforded in the medium to long term against this disease and its variants.
• How does this compare with immunity gained by natural infection against Covid?
• BBC journalists ask the question as to whether there are marked differences in your immune system after a natural infection with coronavirus and after vaccination. 
• The data analysis attached at Appendix 1, based on Government data from the current Delta surge in Israel, suggests that natural infection from prior Covid provides on average 10 times GREATER protection against Delta infection as compared to two shots of the Pfizer mRNA vaccine.
• The 10 times greater protection from Delta for those fully vaccinated appears to be a function of age, and increases from 4-8 times greater protection in the 20-40 age group, to 20-30 times greater protection in the over age 60 group - the most vulnerable age for serious Covid complications.  

Conclusions:

1. Double vaccination with Pfizer’s Covid vaccine does NOT prevent most infections by Delta, although it does substantially reduce the risk of hospitalization for serious illness.
2. As the vaccine does not prevent infection by Delta in many cases, or its further transmission by the infected person, the concept of achieving ‘Herd Immunity’ against Delta with this vaccine is moot. Current policies are largely based on achieving herd immunity.
3. Recovery from a prior natural infection with Covid provides protection against the Delta variant which is 10 times more powerful than the protection provided by two shots of the current Pfizer Covid vaccine.
4. Vaccines based on the whole virion (Whole Inactivated Virus - WIV vaccines) are more similar to natural infection from Covid, in exposing the immune system to the whole virion, and not just to the Spike protein.
5. Data from countries which rely substantially on WIV vaccines are not experiencing a Delta surge comparable to those countries which have relied predominantly on Spike protein-only vaccines.

Refana believes that the above data strongly support the following hypotheses:

• a whole virion (WIV) vaccine creates an immune response that is much closer to actual infection from Covid, as compared to vaccines relying solely on the Spike protein
• a whole virion WIV vaccine will therefore provide significantly higher protection against the Delta surge
• that any Covid vaccine modelled directly on the Delta variant will provide more protection than the SAME vaccine modelled on the much earlier Wuhan strain (i.e. all current vaccines)
• that an ideal vaccine should be able to carry 'multiple payloads' as there will be further evolution of new variants, most likely continually derived from the now dominant Delta strain

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Appendix 

Calculation of the comparable protection against breakthrough Delta Infection: Two shots of Pfizer Covid Vaccine vs Recovery from prior natural infection with Covid.

Number of Double Vaccinated people in Israel:  5.4 million
Number of Recovered people in Israel from Natural Covid Infection:  900,000
Ratio of Double Vaccinated to Recovered:  6:1 (This is the scaling factor of 6)

1. All the crude data is provided in the reports of the Misrad HaBriut, the Israeli Ministry of Health
   The 0-19 age group has been ignored as any age can get Covid, but only certain ages in this cohort can be vaccinated, therefore ratios in this age group are not meaningful
   
2. Column 2 shows the number of fully vaccinated persons in each age group, and total, who have had breakthrough infections since the arrival of Delta, dated from 31 May 2021
   
3. Column 3 shows the number of people who had recovered from a prior Covid infection but nevertheless got a breakthrough infection following the arrival of Delta.
   
4. Column 4 calculates the ratio of breakthrough infections in the fully vaccinated population compared to the number among people who have recovered from a prior Covid infection. This number is gross however as it does not take into account the fact that there are 6 fully vaccinated people in Israel for every 1 person who has recovered from a Covid infection.
   
5. Column 5 calculates the Relative Protection Multiple of recovery from Covid infection compared to full vaccination with two shots, scaled for direct comparability by dividing the gross ratio in Column 4 by 6.
   
6. These figures show that on average prior natural infection by Covid provides 10 times the protection against a breakthrough infection from the Delta variant than vaccination with 2 shots of Pfizer Covid vaccine. 
   
7. While the average relative protection multiple is 10, the effect is highly correlated with age, whereby those over 60 enjoy 20-30 times the protective effect against a breakthrough Delta infection compared to full vaccination
   

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Author: Brian Maccaba, CEO, Refana Inc.  
​Email: Brian@Refana.com  Tel: +972-50-6613672

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