Lots of questions about the Astra Zeneca results. Why different results for the sub-sets? How does it work to have a lower dose protect better? My understanding as below, could have imperfect numbers. 1/11

The 1st vaccine trial COV002 is in the UK. Single blind, multi-site phase II/III study in 12390 adults who got 1 or 2 intramuscular doses of a half dose (~2.5 x1010 viral particles) or full dose (~5x1010 viral particles) of AZD1222 or comparator, meningococcal vaccine. 2/11

The 2nd vaccine trial COV003 is in Brazil. Single blind, multi-site phase II/III study in 10300 adults who got 2 doses of full dose of AZD1222 or comparator, meningococcal vaccine and saline. 3/11

In both suspected cases presenting with compatible symptoms were tested for virological confirmation by COVID-19 PCR. In addition, in the UK weekly swabbing is done for detection of infection and assessment of vaccine efficacy against infection. 4/11

In the UK, when AZD1222 was given as a half dose, followed by a full dose at least one month apart (n=2,741) was vaccine efficacy of 90%. In the 2nd regimen, when 2 full doses were given in Brazil 1 month apart (n=8,895) the vaccine had 62% efficacy in preventing COVID-19. 5/11

No severe cases among the 131 cases analysed so far. Combined analysis from both dosing regimens (n=11,636) resulted in an average efficacy of 70%. All results were statistically significant (p<=0.0001). Decrease in infection seen in the UK. 6/11

Why different results? Populations differ in prior exposure, current exposure, genetic background & host of other factors. Much data needed to understand whether this is just a UK/Brazil difference. Trials ongoing in Japan, Russia, South Africa, & Lat America, target 60,000. 7/11

How come less is more efficacious? Possibly less adenovirus first time around resulted in lower immune response that did not block response to second dose. Or prime-boost. 8/11

Prime-boost vaccine strategies try to enhance cellular and antibody immunity for longer and stronger protection. Can be homologous (both same vaccine) or heterologous (different vaccines). 9/11

Prime-boost is complicated. Selection of antigen, type of vector, delivery route, dose, adjuvant, boosting regimen, the order of vector injection, and the intervals between different vaccinations influence outcome. 10/11

Is it at play here? Possible. but bottom-line is Astra Zeneca's vaccine works and well. Can we improve its performance? Very possible, there is a lot we do not understand about human immunology. The pandemic is making us learn and fast. 11/11