Step 1: Collect Swab Samples
Collect up to 200,000 swab samples from all the global hotspots. Focus on mild cases and pooling.
Use a home sampling approach from volunteers similar to that used by
SCAN. Step 2: DNA Sequencing
DNA sequencing all positive swab samples to determine viral genome of each strain.
Requires about 10% of the capacity of a single 48h run on a modern instrument!
Step 3: Search for Mild Mutants
Search genome sequence data for the right mutant type.
Deletion mutations in accessory genes – e.g. E protein. STEP 4: RAPID TEST
Modification of current RT-PCR based tests for mutant strain detection ensures that the test can be deployed rapidly without compromising speed and accuracy of tests. Allows for more cases infected with the mutant strain to be quickly found.
STEP 5: COMMUNITY SCREENING
Steps 1-4 are relatively quick, easy, and cheap. Step 5 involves searching for more infection cases in the local area around the index case.
Will involve going door-to-door and collecting swab samples from as many people as possible.
Use increasing search rings.
First house, then street, then neighborhood, then whole city (if needed).
STEP 6: MONITOR CASES
Each case found needs to be monitored for clinical outcome.
Ideal: All cases mild and none end up in hospital.
Use “worse than the flu” symptoms (5-10% cases) as a proxy.
STEP 6A: SCALE UP
Complex but known process
Example: Oral Polio Vaccine
Wise to run this in parallel with Step 6
STEP 7: APPROVAL OF THE VACCINE
Ultimately a regulatory decision as to how much data is required. May require further large scale Phase III testing.
Decisions likely to be made independently by each country. Interested in the Science Behind the Approach?
Somewhat radical approach
May fail to find the right strain if the screening size is too small
Usual safety challenges with live attenuated vaccines
Much faster than other approaches
Herd immunity that actually works
Turns SARS-CoV-2 into the common cold
Promote concept to gain political and social support.
Run small scale test program.
Recruit volunteers for
testing. Daniel Tillett, PhD Explains the SANE Approach
High morbidity ~5-10%
High asymptomatic rate ~50%
Little population herd immunity
Why not just new drug treatments?
Herd immunity will take a longtime/never to develop
High cost–what about poor countries?
Yearly and Sporadic Outbreaks
Large crowds will remain dangerous for some time
There’s a risk of a more deadly strain arising.
1918-1919 Influenza Pandemic
Massive safety/regulatory hurdles
Animal > Phase 1 > Phase 2 > Phase 3 > Production
Joker in the pack –
Antibody Dependent Enhancement
Vaccine could make the disease worse
ADE seen with SARS-CoV-1 animal model vaccines
Need to try as many approaches as possible
It is based on a simple hypothesis.
There are natural strains of SARS-CoV-2 in the world that have mutated to be non-pathogenic (asymptomatic or mild), but which are still infective and will provide immunity to the more pathogenic (deadly) strains. One of these natural attenuated strains could be used as a live vaccine and its safety demonstrated using epidemiology via its natural transmission.
Search for an Attenuated Natural Strain via Epidemiology
Most viral vaccines are live attenuated vaccines.
Almost all attenuated vaccines have been created in the lab.
Exception – Sabin Live Polio Vaccine
Strain 2 is a natural strain isolated from a child with mild illness.
Why aren’t there more examples?
Hard to find stable natural attenuated viral strains
Recent technical advances in genomics make this a possibility now.
Almost certainly yes!
Key to the search is using genomic sequencing
Genomics allows us to efficiently sequence 100,000s of individual virus strains for the right mutations.
Genomics is like looking for a needle in a haystack with a large magnet!
If we find a natural attenuated strain with the right type of mutation, how can we show this strain is safe?
Use epidemiology to run what is in effect a human phase III trial performed by nature.
Search for more cases in the local area around the index case and monitor their clinical outcome.
If 100s–1000s people are infected with the strain and all have mild illness then we know the strain is safe.
Check serology to ensure immune response cross reacts and provides protection to the wild-type dangerous strains.
We can use what nature has provided to jump over all the early stage trial phases since we are starting at Phase III.
Slice at least 12 months off the development time for a vaccine!
SANE’s proposal to use live attenuated virus is a well-proven approach to vaccine success. Other Benefits
Vaccine will be simple to produce and administer.
Natural spread to non-vaccinated individuals will increase herd immunity in poor countries and conflict zones.
Set up an ecological battle between the dangerous and mild strains favoring the mild strains leading to extinction of the dangerous strains.
Strain ideal as a challenge strain for other vaccine approaches.