Tue, 05/26/2020 - 12:37
Dear colleagues,
- To start with a lighter note: see the nice cartoons about COVID:
- Chinese Adenovirus COVID vaccine: We knew already about 2 recombinant Adenovirus-based SARS-Cov-2 Spike candidate vaccines in development:
- Janssen, in collaboration with Harvard: Ad26 (= rare human serotype), was already successfully used as a construct with EBOLA envelop (AD26.ZEBOV). https://www.precisionvaccinations.com/vaccines/janssen-adenovirus-based-covid-19-vaccine
- Astra-Zenica, in collaboration with Oxford, will use a Chimp Adenovirus. See https://www.astrazeneca.com/media-centre/press-releases/2020/astrazeneca-advances-response-to-global-covid-19-challenge-as-it-receives-first-commitments-for-oxfords-potential-new-vaccine.html
As far as I can see in PubMed, there are no formal publications yet on these candidates
The paper in attachment is about a similar construct, based on the common human Adenovirus-5, developed by a large Chinese consortium. It shows that this vaccine is well tolerated and that 1 injection also induces immune responses.
- Neutralizing antibodies are induced in up to 75 % of participants, but at rather low titre (Table 3 p. 6).
- CD4 and CD8 T cell responses are induced at 0.1-1 % level, with some polyfunctionality. There is a clear, but limited mitigating effect of previous exposure to Ad5.
Clearly, these responses are not yet optimal. A rare human serotype (Ad26) or a Chimp Ad have the advantage of no pre-existing immunity, but it remains to be seen whether they induce similar immune responses after 1 injection.
A (Ad) prime- (S protein) boost might be a solution, but it is not really discussed by the authors.
As you might remember, the STEP HIV vaccine trial was also based on an Ad5 construct and not only failed to show protection, but even enhancement in those participants with pre-existing Ad5 antibodies. This is not immediately applicable for SARS-CoV-2, as T cells are not targets.
There is also the rather theoretical risk of antibody-dependent enhancement upon infection with the SARS-CoV-2 virus.
- Importance of superspreading is becoming more clear. See Comments in Science. Besides the R0, you have to consider k (dispersion factor): the lower k, the higher the contribution of superspreading.
- According to Kucharschi 10 % of cases lead to 80 % of the spread.
- Superspreading occurs mainly indoors: importance of areosols?
- Importance of speaking loudly, singing
→ Avoiding large indoor gatherings, where people shout, may curtail the epidemic
- An economist view on lockdown, testing and exit. Some quotes:
- Presenting lives versus livelihoods as a dichotomy is used in defence of leaders who hesitated to impose a lockdown……. “If you know you are going to shut down the country eventually, there are huge returns to doing it quickly,”
- If you urgently need masks or ventilators, then there’s no time to put it out to tender and let market mechanisms make the choices…. There must be centralized decision-making and allocation, even if that risks a degree of ‘inefficiency’.
- “Countries and regions that were able to test, trace, and then isolate the infected were able to contain the virus quickly and reopen their economies sooner”
- …we now need to “invest in the testing economy”, for example to establish who can safely return to work and to monitor workplace safety.
- …how innovation in vaccine development can be motivated without reliance on market forces and patenting of what is so clearly a global public good.
Best wishes,
Guido