Despite its advantages over other vaccine technologies for Covid-19, adenovirus vector vaccines are likely to be tripped up by pre-existing antibodies to the vectors used and the need for a second injection to boost protection.

CanSino Biologics’ Ad5-nCoV and Johnson & Johnson’s AdVac platform-based vaccine use a human adenovirus vector, but a significant chunk of people may already have neutralising antibodies against the vector, decreasing efficacy prospects. Phase I Ad5-nCoV data is also underwhelming, adding credence to the issue of pre-existing antibodies.

AstraZeneca’s AZD1222 and Rome-based ReiThera’s Covid-19 vaccines are also adenovirus vectored but use nonhuman vectors. However, AZD1222’s recent animal data also leave questions about its utility to prevent virus spread. A possible way to improve efficacy is to add a booster shot down the line, perhaps using a different adenovirus vector or even a different vaccine technology. Perhaps AZD1222 only carrying SARS-CoV-2’s spike protein may not be enough.

There are at least 38 companies or universities with a recombinant adenovirus-derived vaccine asset for Covid-19 from preclinical to Phase II/III stages, according to GlobalData. AstraZeneca partnered with Oxford University on 30 April to further develop AZD1222, and on 3 June, the US Federal Government’s vaccine initiative, Operation Warp Speed, named it as one of five finalists along with Johnson & Johnson’s (J&J) candidate. Phase I/II AZD1222 trial (NCT04324606) data are expected shortly, while J&J’s Phase I/IIa will start in July. ReiThera will also begin a clinical investigation in the summer. CanSino is the only company that has released clinical trial data, with Ad5-nCoV already in a Phase II trial (NCT04341389) that has a primary completion date of January 2021.

AZD1222 is concurrently in Phase II/III trial (NCT04400838), with data timelines dependent on community viral transmission rates, the Oxford University website states. A registrational field trial expected to start in the summer is likely to require around 25,000–30,000 volunteers if the annualised incidence rate is 1.5%, this news service reported on 14 May. While a challenge trial design could be considered to quickly gather protection data, such a trial design also has its own operational and ethical issues.

Image Credit: Envato/ Amanda Scott

News This Week