The SANE Approach
SANE's 7-Step Process
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
- 1950s technology
- Complex but known process
- Example: Oral Polio Vaccine
- 25c/dose
- 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?
- Read the science behind The SANE Approach.
- Read the FAQs and common misunderstandings.
- 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
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- Airborne
- High morbidity ~5-10%
- High asymptomatic rate ~50%
- Little population herd immunity
- Asymptomatic/pre-symptomatic spread
Why not just new drug treatments?
- Vulnerable people
- 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
Time Frame
- 18 months to never
Why?
- 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
- Regulatory caution!
- 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
Yes
- 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.
