The WHO interim recommendations for the use of the Oxford/ AstraZeneca Vaccine is very welcome. They are very much aligned to what our own TGA recommended for the Pfizer vaccine, and indeed it is likely to be similar to what will be recommended by the TGA for the Oxford/ AstraZeneca Vaccine, once it is approved. It is totally appropriate that Health Care workers and the Elderly are given priority as the incidence of COVID in the healthcare workers is high, and the elevated mortality in the elderly is well documented.

The published recommendation by the WHO for the use of the Oxford/AstraZeneca candidate in target groups including health care workers and the elderly is based on a review of substantial evidence available to date. The document explains the role of this vaccine candidate in a number of specific populations and should therefore hopefully serve to clarify the situation with this vaccine at this point in time.

Recently there have been a number of reports that have raised concern by some including suggestions of reduced efficacy against the South African variant (B1.351) however it is well explained in this document that these reports are based on a small sample size, that indirect evidence is still compatible with protection against severe COVID-19 and of course that ongoing evaluation is required and underway.

It also addresses other populations in which there have been many discussions including persons aged 65 and over. The primary issue with this population has been the relatively small number of participants in this age group in the clinical trials and therefore the relatively low number of cases preventing conclusions being drawn, not that there was any suggestion there were concerns over its safety or efficacy in this group. In actual fact the immune responses induced by the vaccine in older persons is well documented and similar to those in other age groups and more precise efficacy estimates for this group are expected soon also.

Concerns of its relative lower efficacy compared to other vaccines are also addressed by the more recent data suggesting higher efficacy with a greater interval between doses. Hence the recommendation in this document is for 2 doses separated by 8 to 12 weeks.

Hopefully, these recommendations and the clear explanation of the current situation with respect to specific populations included in the document should adequately address the majority of concerns relating to this vaccine raised in recent times and clarify its use moving forward.

The WHO SAGE recommendations for the AstraZeneca vaccine are very welcome. They recommend the use of the vaccine in all ages over 18 including the elderly. Globally, there is a major issue with equity in vaccine access and roll out. The AZ vaccine will reduce inequity as the company is committed to global access; not to profit during the pandemic, and has established many plants to manufacture the vaccine worldwide including the CSL facility in Melbourne. COVAX is about to release the AstraZeneca vaccine to many countries, including up to 30% of allocations to some of the smaller Pacific island countries.

The vaccine efficacy against COVID related hospitalisation is 100%, there were no deaths and no severe COVID in the vaccinated groups. The VE against symptomatic infection was 63% (51%,72%). However, the dosing intervals varied between studies and a longer dosing interval between dose 1 & 2 was associated with higher immunogenicity & higher VE (78%). Therefore it is recommended that doses are administered 8-12 weeks apart. VE in those with comorbidities was 62% (42%, 75%). For the elderly, VE was about 50% but there was less precision around these findings as there were few old people enrolled in the study. Importantly, the elderly received doses <8w apart which now we know is a suboptimal schedule but their immunogenicity was similar to younger ages. The US study is still enrolling but will have more data soon in the elderly. Additionally, within the next few weeks, there will be vaccine effectiveness data from the UK with the national rollout. These studies use a longer dosing interval and therefore it is likely to be efficacious in the elderly with optimised dosage intervals. Importantly, modelling suggests that vaccinating >65y to reduce mortality is a priority even if VE is lower, especially if no other vaccine is available. 

The data presented at the SAGE meeting suggests but does not prove a reduction in transmission. This is extremely important as an effect on transmission will be one of the key determinants of herd protection.

The vaccine is safe.

With the variants: 
B.1.17 (UK) variant: VE has been preserved: 75% (42-89%). 
501Y.V2 (B.1351 South African) variant: The RCT in South Africa was powered to show 60% VE against mild-moderate COVID-19. No VE was found against mild-moderate infection but there were wide confidence intervals. The study was not designed to assess VE against severe COVID but this is plausible as antibody (nAb) data is similar to the Johnson & Johnson vaccine which found a VE of 89% against severe COVID in South Africa.

In summary, this is a safe and effective vaccine against the original (wild) strain and the B.1.1.7 (UK) strain. Despite not being effective against the 501Y.V2 (South African) strain there are good reasons to believe that may be effective against severe COVID as it uses a similar platform to the Johnson & Johnson vaccine. With the new strains in mind, AstraZeneca are modifying the strain and planning on doing studies using sequential dosing with Sputnik V vaccine (other viral vector vaccine) to improve its efficacy.

With a global supply issue and an effective, affordable vaccine available, it is critical this vaccine is authorised for use.