The SANE Approach

Natural vs Lab Attenuated Strains

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!
DNA Sequencing

Step 3: Search for Mild Mutants

  • Search genome sequence data for the right mutant type.
  • Deletion mutations in accessory genes – e.g. E protein.
Genome Sequencing


  • 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.
Rapid Test


  • 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).
Community Screening


  • 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.


  • 1950s technology
  • Complex but known process
  • Example: Oral Polio Vaccine
    • 25c/dose
  • Wise to run this in parallel with Step 6
Scale Up


  • 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.
Polio Vaccine Campaign

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

Learn More

  • 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


  • 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


  • 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.
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