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July 25, 2020

Can Antibodies Be Used to Treat Covid-19?

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.

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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."

July 22, 2020

Covid-19 Vaccine Development Update

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: 

 

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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. 

 

July 18, 2020

Will We Really Have a Vaccine for Covid-19 Soon?

I recently wrote about the 3 phases of Clinical Trials that must be completed to apply for FDA approval.  The mumps vaccine was created in 4 years - and set the record for vaccine development.  The average time is 7-10 years.  There are 150-160 vaccines being developed right now and 30 vaccines are in the pipeline. 

Read more below collage:

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Phase 1 trials are small - to test different doses and assess the safety of the vaccine.  There are 15 vaccines in phase 1 trials.

Phase 2 trials have hundreds of volunteers and safety is still being assessed.  But vaccine effectiveness and antibody production is measured in the vaccinated vs placebo groups.  There are 11 vaccines in Phase 2 trials.   

Phase 3 trials still assess safety, but the effectiveness to prevent Covid-19 in 30,000 or more volunteers will be compared to a placebo group.  There are 4 vaccines in phase 3 trials: including one UK (Oxford), 2 Chinese, and 1 Australian  company (Data taken from NYT vaccine tracker).

The US front runner vaccine is from Moderna-NIAID/NIH and it will begin Phase 3 on July 27th.  The Oxford University/AstraZeneca vaccine is being supported in part by the US Gov't and both will be available in the US after approval. The number of Covid-19 cases and deaths are still in exponential growth in the US and companies are going to develop millions of doses for some of the vaccines, even before FDA approval is complete.   This is a huge financial risk for pharmaceutical companies and we can only hope that distribution will also be discussed and planned before approval is granted.  Until then we need to learn how to live safely with the virus. 

July 15, 2020

When Will the Pandemic End?

We either need a vaccine or miracle drugs to treat Covid-19.  All drugs must complete Phase 1, Phase 2, and Phase 3 Clinical Trials before applying for FDA Approval - just like vaccines which I wrote about several days ago.  These are also usually small, medium, and large trials. Phase 1 is to determine drug dose and SAFETY, Phase 2 determines drug dose, SAFETY, and efficacy.  The final big Phase 3 trial is a randomized controlled trial, double blind, with a placebo group or a group that is taking the current best drug for the disease for comparison.  This trial is primarily to study EFFICACY and safety. The major difference between the vaccine and drug trials is that volunteers who are testing a drug must have a firm diagnosis of Covid-19.

Continue reading below image. 

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There are only two drugs which show efficacy against Covid-19 - dexamethasone and remdesivir  - and neither is a newly developed drug.  Dexamethasone decreases mortality by 1/3rd in patients on ventilators, and 1/5th in patients only on oxygen.  Dexamethasone, a powerful steroid, is directed at the inflammatory response to coronavirus in the lungs - called "cytokine storm."  Remdesivir, an anti-viral drug, shortens the length of the illness by several days. There are news articles about both drugs in the press and often in financial reports.  Both of these phase 3 drug trials are also now published as pre-prints.  Neither has yet been published as a peer-reviewed scientific journal publication.  Beware of the hydroxychloroquine press releases to date.  

Anyone who has read all the way to the end of this blog post may wonder why my blog posts now discuss science. I am a retired medical school professor of internal medicine and hematology (40 years) - and always enrolled patients on vaccine (pneumovax) and cancer drug trials for leukemia, lymphoma, and myeloma.  I'm not an epidemiologist or infectious disease specialist - and I rely on experts in these fields to lead the way through our SARS-Cov-2 pandemic.  We must learn to live with this virus until a vaccine is available for prevention or better drugs are developed for treatment. 

July 11, 2020

Roll Up Your Sleeve!

My healthy volunteer is enrolled in a vaccine trial which has 3 separate Clinical Phases before FDA approval.

Phase 1 usually has less than 50 healthy volunteers, in the age range of the proposed treatment group.  This phase is to test for SAFETY of the vaccine.  Several concentrations of the vaccine will be tested to determine the best dose(s) for Clinical Phase 2.   Antibody production after the vaccine may be assessed in a subgroup.  Subjects may be given 1 or 2 injections one month apart. Adverse effects are recorded and subjects followed for several months or a year.  Read Phase 2 and 3 below.

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Phase 2 has many more healthy volunteers - usually in the hundreds.  Several concentrations of the vaccine may still be tested and 2 injections may be given 1 month apart.  The main goal of this phase is still assessing SAFETY, but some subjects will also be tested for the development of antibodies.  Subjects are usually randomized between treatment and placebo groups.

Phase 3 has thousands or tens of thousands of healthy volunteers randomized between the vaccine and placebo.  It may also be "double-blind" so neither the treated subjects nor the placebo group know what injection they received.  In this phase EFFICACY of the vaccine is assessed - usually by measuring antibody titers, the presence of neutralizing antibodies that prevent virus multiplication, and cases of Covid-19 in the vaccinated vs placebo groups. Safety is still assessed.  After the Phase 3 trial is analyzed, the data can be presented to the FDA for vaccine approval.  The FDA won't approve a vaccine unless it protects at least 50% of the treated group and would love to see even higher efficacy.

Only a few of the 150+ vaccines being developed will be in Phase 3 this Summer and Fall - and the leading vaccine trials will enroll at least 30,000 healthy volunteers randomized between vaccine and placebo.  The study sites selected must still have enough coronavirus virus transmission so the effectiveness of the vaccine can be measured. That shouldn't be a problem in the South or West in the US.