straZeneca/Oxford University and CanSino publish promising Covid-19 vaccine clinical trial data, but too early to declare a winner

On 20 July, AstraZeneca and Oxford University published Phase I/II results of their Covid-19 vaccine candidate ChAdOx1/AZD1222, and Chinese biotech CanSino published Phase II results of its Covid-19 vaccine candidate Ad5-nCoV.

In the AZD1222 study, 1,077 healthy adults, 18–55 years of age, were randomised to receive either a single dose of 5×10¹⁰ viral particles of AZD1222 or a meningococcal MenACWY vaccine; ten patients received a second dose of the vaccine.

Viral receptor-binding and neutralising antibodies were detected after 28 days, as well as viral protein-specific T-cell responses. Mild and moderate adverse events like injection-site pain and tenderness, as well as fatigue, were more common than in the MenACWY control group; no serious side effects were reported.

A sub-group that received paracetamol with the vaccine showed reduced reactogenicity. The 1% of trial participants who received a second dose of the vaccine showed 3–6x more viral protein antibodies and AstraZeneca said it will continue with two doses for the Phase II/III studies.

In CanSino’s Ad5-nCoV trial in China, 508 healthy adults were randomised to receive a 5×10¹⁰ or a 1×10¹¹single vaccine dose or placebo. Receptor binding domain (RBD) antibodies were detected after 14 days and peaked after 28 days with 96% and 97% of participants showing seroconversion. In the placebo group, no antibody increase from baseline was detected.

Seroconversion of neutralising antibodies occurred in 59% of subjects who received the higher vaccine dose and in 47% on the lower dose. Positive specific T-cell responses were found in 90% (high dose) and 88% (low dose) of participants.

After 14 days, 72% and 74% of participants in the high and low-dose vaccine group, respectively, showed adverse events (AE), versus 37% in the placebo group. Most AEs were mild and only 9% severe; no serious AEs were reported after 28 days.

However, in 52% of study participants who had high pre-existing immunity to the human adenovirus vector, both types of antibodies were only at half the level of the group with low pre-existing immunity. A second dose of CanSino’s vaccine might solve this issue, but on the other hand, reduce the number of people who can be vaccinated.

Furthermore, trial participants older than 55 years of age showed lower antibody responses than younger participants, possibly correlated with higher pre-existing Ad5 immunity, which is a serious issue since older people are particularly vulnerable to SARS-CoV-2 infections.

While the data from both trials are encouraging, we have now seen promising data from multiple companies.

It is not yet clear who is in the lead, as immunogenicity and B-cell and T-cell responses are nice to see, and support continued development, but none of these data paints a clear picture of a winner. There is ultimately one key piece of data that we are waiting on – protection against disease.

Protection is not a simple binary endpoint that answers a single question, such as ‘did people get the disease or not?’ A vaccine could be not very effective in reducing prevalence, but have significant effects on reducing morbidity and mortality.

Furthermore, one vaccine could be better at preventing disease in older patients and those with comorbidities who are might likely to suffer severe effects from Covid-19, and another confer protection for a significantly longer period of time. These questions all take time to answer and must be properly interrogated through clinical trials.

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