Paper and Threads

New York Times Aug 2:  "Scientists Worry About Political Influence Over Coronavirus Vaccine Project"  A horrifying article!  "Emergency Use Authorization" to make vaccine available in October, before the Phase 3 vaccine trial is complete, and that is required for FDA approval.  Continue reading....

This is long, but really important.  I am writing as a retired MD, who has experience with Clinical Trials for cancer treatment.  It is dangerous to make assumptions on Trial conclusions from incomplete data. 

There is great fear that there will be political pressure to release the front runner vaccines in October with an emergency use authorization (EUA).  I watched 6 hours of hearings by the House Energy and Commerce Subcommittee several weeks ago, and the 5 Vaccine Company representatives were asked over and over how they were going to insure the vaccines will be safe.  I watched an hour long interview of Dr. Stephen Hahn, by Dr. Howard Bauchner, last week.  Hahn is the FDA Commissioner and Bauchner is the editor of JAMA.  The Vaccine companies said that the Phase 3 Trials would not be rushed and safety compromised.  Dr.Hahn said that panels of vaccine scientists just worked on a set of standards that must be met in order to approve a vaccine - and this was done so any decision will be made based "only on the scientific data."

There was a very long article in the New York Times Aug 2nd, that was picked up by other news sites. They say there is a lot of political pressure to get a vaccine approved in October.  It says that if the FDA won't give "Emergency Use Authorization," the secretary of HHS in the White House can overrule his decision.  I recommend caution for the following reasons- and I usually take vaccines without worry.

1.  The two major US vaccines, Moderna-NIAID and Pfizer BioNtech, each began their phase 3 trials the last week in July. Moderna just published results of their Phase 1 Trial in NEJM (peer reviewed).  There were only 45 subjects vaccinated, evaluated, and reported.  They have not yet released their Phase 2 data.  I can't find any data from Pfizer as of today.  I assume they have completed Phase 1 and Phase 2 trials, although volunteers are usually followed for 1-2 years for late side effects.

2.  Moderna and Pfizer are part of Operation Warp Speed, and committed to test 30,000 volunteers in a Phase 3 trial.  Half of the volunteers will be vaccinated and half will get a placebo injection.  But no one will know who received which injection.  Volunteer enrollment just began( July 23 and 27).

3.  Each volunteer will get two doses, days 1 and 29 (Moderna) and days 1 and 21 Pfizer, so if they are enrolling volunteers beginning in August, the last volunteers enrolled will be getting their vaccinations in late August, September or even later.  By October those patients may not be followed long enough to adequately assess safety and efficacy! 

4.  The FDA will require that each vaccine will have a minimum of 50% efficacy (preferably >70%) in preventing Covid-19in the vaccinated group and acceptable adverse effects. Many tests to rate the immune response need to be done in specialized research labs and will take time.  These are blinded studies, and there are oversight committees set up who could stop the study if adverse effects are serious.

5.  If an EUA were granted due to political pressure, I wouldn't get that vaccine until the patients were all enrolled, followed for awhile, and preliminary results analyzed.  I want the vaccinated subjects to have at least 50% protection from Covid-19  when compared to the placebo group - AND side effects to be limited to injection site pain and flu-like symptoms. 

I'd also want to see careful review by other scientists.  The mumps vaccine set the speed record for vaccine development - 4 years. New technology made rapid vaccine development possible - both of these vaccines are made from the coronavirus spike protein genetic sequence and our cells make a spike protein which stimulates our immune system.  Older vaccines were made with inactive viruses or proteins of the virus.

Posted by Shirley at 7:40 AM | Permalink | Comments (1)

Three Vaccine developers began their Phase 3 Randomized Controlled Trials in the last several weeks.  Each of them must enroll 30,000 healthy volunteers.  Half of the group will receive vaccine injections and the other half will receive a saline (salt water) injection as placebo.  Each volunteer will then be monitored for adverse events, and Covid-19.  Subgroups will also be tested for efficacy -both development of antibody titers and neutralizing antibodies that block virus proliferation.  In addition cellular immunity will be assessed by T helper cell activity.  No one will know what shot they received until the end of the trial.

Continue Reading Below:

Evidence of prevention of Covid-19 will be monitored in the treatment and placebo groups and results may depend on the activity of the virus where they are enrolling volunteers.  New York tests 50,000+ individuals each day, but the incidence of positive virus tests is only 1-1.5%.  If volunteers are vaccinated in the states with increasing infectivity, enrollment and protection in the vaccinated vs the placebo group may be faster.  Recently developed FDA guidelines for vaccine approval set the minimum at 50% protection by each vaccine for FDA approval.

BUT there may be political pressure to give "EMERGENCY USE APPROVAL" ("Pre-election Surprise) and then the government would be shortening the observation time for "rare, but significant" adverse effects to be seen.  The FDA commissioner this week said that his decisions will only be based on SCIENCE - and we have to hope that he is a man of his word.

Posted by Shirley at 7:55 AM | Permalink | Comments (0)

We are going to have to learn how to live with this virus until the population is vaccinated, and natural infection increases herd immunity to more than 70%.  Until we can be vaccinated, we MUST practice social distancing, hand washing, and mask wearing.  There is data to suggest that masks keep us from spreading the virus, AND they also limit the amount of virus that we breathe in.  When populations have protected themselves with masks they tend to have mild symptoms or are asymptomatic! See article link below.

On my morning walk I saw two store windows filled with these head mannequins and they had many different types of masks, in many different colors.  There even was a black mask covered in Swarovski crystals! Why do you think that the masks on the left have a narrow sliver hole over the nose? The store was still closed early in the AM, or I would have asked them.  I made masks for my husband and I, and our kids and grandkids that live in NYC.  As my back continues to improve I will make more.  I think we are destined to be wearing masks until 2021.  I love the pattern I used, and will also include a link at the bottom of this post.  Read more below.

This week two companies began Phase 3 vaccine trials.  They each need 30,000 healthy volunteers to determine if the vaccinated and placebo groups have a significant difference in Covid-19infection. Research Labs will also be measuring antibody titers and T cell responses in a cohort of the subjects.  In order to have a definitive answer, infectivity in the geographic area must be high enough to make people sick - the FDA approval requires 50% protection in the vaccinated group - at a minimum.  .

Posted by Shirley at 7:44 AM | Permalink | Comments (0)

When you transfuse antibodies into patients, you develop "passive, instead of natural immunity."  During the 1918 flu pandemic, patients who recovered from influenza donated blood so their antibodies could be transfused into other critically ill patients.  More recently, "convalescent plasma" from recovered Ebola patients was given to other patients.  Randomized control trials (RCT) are being done to test "convalescent plasma" for Covid-19 patients, but in addition MONOCLONAL ANTIBODIES are being developed from blood obtained from recovered patients.   Read about them below the collage.

Patients who have recovered from Covid-19 have naturally occurring immunity against all parts of the SARS-CoV-2 virus.  Their antibodies and immune cells are being studied, and the strongest neutralizing antibodies (which stop viral replication), are used to develop monoclonal antibodies which can be produced in large quantities.  This technology was first developed in the 1970s and is now being used to create many types of therapy, including cancer drugs.  In the classic method, cells which are producing antibodies are fused with a specific clone of antibody producing cells that can be grown in culture.  This clone becomes a protein factory which makes just one potent neutralizing antibody.  There are many monoclonal antibodies being made to SARS-CoV-19 and at least 3 are in early clinical trials.  Passive immunity with monoclonal antibodies is only effective for weeks to a month+, but when administered they can change the course of critically ill patients.  You can usually recognize monoclonal antibodies that are FDA approved because their names end with "ab."

Posted by Shirley at 7:23 AM | Permalink | Comments (0)

There are 2 front runner vaccines being tested in the US - Moderna is a US Company based in Cambridge Mass and Oxford AstraZeneca is based in the UK, but has US financial support.  Both companies finally published their Phase 1 clinical trial results in the last week in peer-reviewed leading medical journals, and both are ready for Phase 3 "huge trials"  which will continue to test safety and will actually test effectiveness in preventing transmission of SARS-CoV-2 to vaccinated subjects.  These trials are prospective, randomized, placebo-controlled trials in not less than 30,000 volunteers per vaccine.  The trials will be "blinded" so neither the volunteers nor the MDs, Nurses, Trial Coordinators etc. will know what injection the volunteers receive.  The Phase 1 trials for both vaccines demonstrated antibody production, especially neutralizing antibodies which block virus replication.  And side effects were like the usual flu shot - mostly related to the injection site and some flu-like symptoms. 

The collage for my pandemic science series today is to celebrate the beginning of Phase 3 trials.  There are more than 140 vaccines being developed, that have not yet begun clinical trials.  As of today 19 vaccines are in Phase 1 and 13 in Phase 2.  Moderna will begin their Phase 3 trial on July 27th.  If you know the 3 phases of clinical trials, you are now better able to read and listen to the continual "chatter" about vaccines.  We aren't there yet!!  And may not be there until 2021.  But until then we will have to learn to live with the virus - and increasing deaths.  Stay home and stay healthy.

Continue reading below the collage: 

The Moderna-NIH Vaccine Research Center vaccine was made with the newest technology.  Instead of using the viruses themselves (usually dead or made ineffective), they made messenger RNA (mRNA) from the virus binding region of the spike protein of SARS-CoV-2 using the structure reported from China on January 10th. Most vaccines were created by making huge amounts of the antigenic proteins and injected them into us to stimulate the immune response.  Now the mRNA is stabilized and used as the ANTIGEN to stimulate our cells to begin the ANTIBODY immune response. 

The mRNA is transported into cells and acts as a blueprint for the cells to make the important part of the spike protein - the part that attaches to our cells and lets the virus in!  The spike protein then stimulates the immune response in the cells in our body and we make protective antibodies! This method cuts years out of the vaccine development process and has been tested in cell cultures, and various animal models- demonstrating that the immune response is able to then prevent the virus from replication in cells in our body.  Both vaccines completed Phase 2 Clinical Trials in hundreds of volunteers. 

This is complicated but very interesting and hopefully we will all get vaccinated, develop "herd immunity," and stop the pandemic.  The Oxford vaccine is using a similar, but not identical process. 

Posted by Shirley at 7:53 AM | Permalink | Comments (0)