COVID-19 Interest Group

                           August 15, 2020

                         CIG Bulletin #18  Vaccines Are Coming, but When?

                                                           By Tina Etcheverry, Berkeley Rotary 

Everyone is talking about vaccines these days, but no one knows when these will arrive to a neighborhood near you.  There are more than 200 companies developing vaccines across the world, and the major 7 companies (more about this later) are in Phase III Trials.  

The results from the earlier Phase II clinical trials are promising, with trial participants developing good immune responses, with only mild reactions like temporary fever, minor aches and sore arms.  The FDA has mandated in the supplemental guidance document 21CSR10.115 (g)(v) that the Phase III studies need to be designed to test 30,000 subjects, in a blinded trial with half of the patients treated with placebo, and the full duration of the trials lasting two years with a 50% reduction in Covid disease.  This response rate is similar to the average effectiveness of flu vaccines.  The two-year period was selected to test across more than one spike of the disease, including multiple flu seasons, and to monitor the duration of the immunity.  This will provide a good safety profile across a broad spectrum of the population (including age, underlying diseases, ethnic background, and gender).  Of course, reports are circulating that vaccines will be available by the end of this year (2020) based on only 4 months of clinical data, so then there must be an opportunity for emergency use authorization (EUA) based on immune response (lab tests for antibodies and T-cells) and not the described primary endpoints of reduction of COVID disease. 

Primary endpoints are (1) prevent symptomatic disease (2) prevent infections measured by laboratory testing with or without symptoms (to include asymptomatic COVID positive).  Secondary endpoints are (1) prevent death (2) measure immune response by blood samples across 2 years and saliva samples tested periodically.  Patients that develop COVID symptoms are instructed to obtain a PCR test within 72 hours.

 Some background…

 Corporate Strategies

The companies developing vaccines have taken different corporate strategies.  Different approaches are listed below. 

• Moderna’s approach is to be the “First to Data”. They were ready with a candidate molecule in February and quickly started their Phase I testing.  They are the first to Phase III and have been releasing data from the earlier studies.  However, they may not be first to a broad market distribution since the mRNA vaccine is difficult to manufacture and has to be shipped and stored frozen.  Also, this is a novel vaccine:  no mRNA vaccine has ever been approved for the commercial market place. 
• Pfizer is also developing a nucleic acid vaccine but taking the approach “Best in Class” by studying clinically 4 different candidate vaccines, and has selected the best molecule for their Phase III studies.
• AstraZeneca/Oxford is playing “Catch-up” by performing a combined PhI/PhII study of 1,000 patients, a much larger study than normal. By having more patients in their early studies they could determine the best dose and broaden safety data that will save time by the end of the trial. 
• Lastly, we have the Russian government releasing a vaccine (Sputnik V) after treating 2,000 people and before safety and efficacy data is widely available. Their approach is to shine on the “Political Stage”.  Who knows?  Maybe this is the best approach of all. 
• The US government is pushing “Operation Warp Speed” which involves commitment to spend $9 billion to start manufacturing of various vaccines before the safety and efficacy data is available. 

Vaccine Technologies

The Table below describes the various vaccine types that are in development.  Of these, only the mRNA-base vaccines from Moderna and Pfizer are completely novel technologies and never been approved for commercial markets.

 Risks

As a final point, it is important to acknowledge that vaccines are not entirely risk free. The primary risks associated with vaccines are potential adverse immune reactions, especially in people with allergies. In the few vaccines where live attenuated virus is used, you can also sometimes get reactivation of the virus to an infectious form. This was known to occur with the oral polio vaccine.  There is also the potential for a hyper-immune response (similar to a deadly cytokine cascade) on future infections of coronavirus with some people carrying vaccine-generated immunity. 

I think it's important to know about these risks because there is so much disinformation about vaccines. The purpose of vaccines is to promote public health through risk reduction, not the complete elimination of health risks. While some people can have adverse reactions to vaccines (particularly if they have immune disorders), in general people are safer for having taken the vaccine. The action of getting a vaccine does carry some small health risk, but it's probably a smaller risk than I take when I drive somewhere in my car.  All activities carry some level of health risk and making informed health decisions is really about minimizing rather than eliminating the possibility of negative health outcomes.

Nature News Feature “The race for coronavirus vaccines”

https://www.nature.com/articles/d41586-020-01221-y

 https://www.washingtonpost.com/graphics/2020/health/covid-vaccine-update-coronavirus/ 

Disclaimer:  The opinions expressed were based on data derived from public sources.  However, these are our opinions and our attempt to assimilate multiple viewpoints.  We do not pretend to be experts in the infectious disease field but bring our expertise from our prior training in science, engineering and medical fields to these issues as interested viewers.