Oxford vaccine animal study results--
Highlights:
- recombinant adenovirus expressing SARS-CoV-2 Spike
- Th1 response in mice
- mixed Th1-Th2 response in macaques
- only partial protection observed
- presumably-contagious nasal viral shedding still occurred
- no VED/ADE
Highlights:
- recombinant adenovirus expressing SARS-CoV-2 Spike
- Th1 response in mice
- mixed Th1-Th2 response in macaques
- only partial protection observed
- presumably-contagious nasal viral shedding still occurred
- no VED/ADE
Moderna paper yesterday:
- fully synthetic
- solely Th1 response in monkeys, no Th2 (good, less VED risk)
- almost fully protective: minimal illness in immunized group
- much less nasal shedding in immunized animals vs. controls
- also no VED/ADE
- fully synthetic
- solely Th1 response in monkeys, no Th2 (good, less VED risk)
- almost fully protective: minimal illness in immunized group
- much less nasal shedding in immunized animals vs. controls
- also no VED/ADE
Although the Oxford study used a marginally larger viral inoculum challenge, overall I would say the winner is pretty clearly Moderna.
The partial Th2 response in the Oxford macaque study is worrisome, suggesting the possibility of rare VED risk.
The partial Th2 response in the Oxford macaque study is worrisome, suggesting the possibility of rare VED risk.
Some context on viral inoculum size:
dhs.gov/sites/default/…
Rhesus macaques seem to require a much larger inoculum than humans or African green monkeys to become infected.
See also:
medrxiv.org/content/10.110…
dhs.gov/sites/default/…
Rhesus macaques seem to require a much larger inoculum than humans or African green monkeys to become infected.
See also:
medrxiv.org/content/10.110…
In terms of comparative viral load:
Recently-infected cats had ~1e3-1e4 PFU/mL in nasal and fecal isolates.
nejm.org/doi/pdf/10.105…
A severe human case also showed ~1e3-1e4 PFU/mL in isolates from nasal, bronchial, and fecal samples:
wwwnc.cdc.gov/eid/article/26…
Recently-infected cats had ~1e3-1e4 PFU/mL in nasal and fecal isolates.
nejm.org/doi/pdf/10.105…
A severe human case also showed ~1e3-1e4 PFU/mL in isolates from nasal, bronchial, and fecal samples:
wwwnc.cdc.gov/eid/article/26…
Based on these results, I suspect the 'minimum' infectious inoculum size in humans may be much smaller than 1e3 PFU.
Regardless, it is likely better expressed as a conditional probability of infection as a function of inoculum and route of exposure than as a minimum per se.
Regardless, it is likely better expressed as a conditional probability of infection as a function of inoculum and route of exposure than as a minimum per se.
I think a model having a large number of very small inocula, like sparks falling on something flammable, is likely more accurate than a single large exposure.
No one inhales an entire milliliter of infected secretions, so 1e3 PFU minimum inoculum cannot possibly be accurate.
No one inhales an entire milliliter of infected secretions, so 1e3 PFU minimum inoculum cannot possibly be accurate.
@halvorz curious if you have any thoughts on the inoculum size results reported above.
