Modernized variolation

Radvac is working to bring back and modernize variolation by applying advances from the sciences of virology and immunology.

How modernized variolation self-experiments are structured

Collect

A sample is taken from a donor who is confirmed to be ill. For a respiratory virus that usually means nasal mucus, which carries a high pathogen concentration in the first few days of symptoms.

Inactivate or attenuate

The pathogen is rendered unable to replicate — or slowed so that it replicates poorly. Radvac's current focus is hydrogen peroxide, which disables pathogens while partly preserving the antigen structures the immune system needs to see.

Administer

The treated sample is self-administered by a route chosen to stimulate immunity. Adjuvants like Neomycin, Polymyxin B, and β-glucans are used to amplify the immune response.

Monitor

Outcomes and any side effects are recorded for several weeks.

Measure response

The goal is to stimulate an immune response resembling natural infection without the illness: mucosal antibodies at the point of entry plus systemic immunity. This can be verified by sequencing the pathogen's genome and then blood testing for appropriate antibodies.

Modernized variolation vs conventional vaccines

Category	Modernized variolation	Conventional vaccines
Speed of deployment	Can be deployed immediately at the site of an outbreak.	Take years to be developed, manufactured, tested, approved by regulatory bodies, and widely deployed.
Match to current variants	Uses the pathogen actually circulating, so it is inherently matched to that variant	Typically target older variants that existed at the start of the vaccine development process
Regulatory requirements	Self-administration does not require regulatory approval	Require regulatory approval, an expensive, multi-year process
Cost	Potentially very low-cost and locally deployable	Often expensive due to R&D, manufacturing and distribution
Safety	Can be made very safe using accessible inactivation technology.	Generally very safe
Similarity to natural infection	Mimics natural infection, minus the illness; broader immunity	Often induces narrower responses; depends on platform
Mucosal immunity	Typical routes of administration should induce mucosal immunity	Licensed vaccines (e.g. mRNA) induce weak mucosal immunity
Public acceptance/hesitancy	May be more acceptable to individuals skeptical of conventional vaccines	Hesitancy exists due to distrust, past public health missteps, misinformation, and perceived risks.

Routes under investigation

Intranasal

Via spray, nebulizer, or insufflation. Over 90% of respiratory pathogens enter through the nasal mucosa and respiratory tract, so this is the route that Radvac self-experimenters are studying first.

Transdermal

A microneedle roller or array carries the inoculum past the stratum corneum into the dermis. This is the modern equivalent of the dermal route that became standard for smallpox variolation. Rollers with sterilizable titanium needles can be purchased for under $20.

Oral cavity

An H₂O₂-inactivated sample is placed around the gums and then flossed in place targetting the gingival sulcus. A similar approach was recently shown to drive both mucosal and systemic immunization in animal models.

Enteric capsule

A capsule that protects its contents from stomach acid and releases them in the gut. Yeast is a potential adjuvant, in line with other Radvac work.

Illustration

Six-panel diagram of an intranasal modernized variolation procedure: nasal mucus is collected from an ill donor into a tube, hydrogen peroxide is added, the tube is mixed, the treated inoculum is drawn up, then administered into the nose of a recipient, with a cutaway showing it reaching the nasal mucosa.