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AstraZeneca’s vaccine results suggest a modality-independent dip in protection against variants

Plus AZ-Oxford vaccine to be tested in combo with Pfizer-BioNTech’s Comirnaty and Russian vaccine Sputnik V

Feb 6, 2021 | 2:56 AM GMT

AstraZeneca is the latest company to report that its COVID-19 vaccine seems to be working against new variants of the virus, just not quite as well. So far, that effect has been independent of the vaccine modality.

The latest data analysis from the COV002 U.K. pivotal trial of COVID-19 AstraZeneca (AZD1222), the adenoviral vector vaccine developed by AstraZeneca plc (LSE:AZN; NASDAQ:AZN), revealed only a small decline in protection against an emerging SARS-CoV-2 variant.

It mirrors the difference Novavax Inc. (NASDAQ:NVAX) found for its protein-based vaccine, and indicates similar magnitudes of weakened protection across modalities.

AstraZeneca reported 74.6% (95% CI: 41.6, 88.9) efficacy against symptomatic disease caused by the B.1.1.7 (501Y.V1) variant first identified in the U.K. in a Lancet  preprint published Feb. 4. The vaccine was 84% (95% CI: 70.7, 91.4) effective against non-B.1.1.7 variants.

That 9.4% difference between protection against B.1.1.7 and other variants is on par with the 10% spread for Novavax’s NVX-CoV2373. In data from a Phase III U.K. trial released on Jan. 28, Novavax reported 85.6% efficacy against B.1.1.7 and 95.6% against the original variant.

The variant-based paper also support findings reported Monday in a Lancet paper that showed the vaccine reduces overall, but not asymptomatic, COVID-19 case numbers.

The new analysis of AZ’s vaccine readout didn’t have enough data from asymptomatic individuals to make a conclusion on the B.1.1.7 variant, but showed 15.7% efficacy across all cases based on 208 sequenced and unsequenced cases.

Though the vaccine had little effect on the number of asymptomatic cases in the study, the report includes viral load data, which plays into whether a patient can spread the disease. The asymptomatic patients in the vaccinated and control groups appear to have largely overlapping viral loads, but the study reports a statistically significant difference (p=0.004).

The results bolster the suggestion that the vaccine does little to bring down the number of asymptomatic cases but raise the possibility that the vaccine’s ability to reduce viral loads, and therefore prevent asymptomatic patients from spreading the infection, may be limited. 

Mixing and matching vaccines

COVID-19 Vaccine AstraZeneca (AZD1222) is poised to be evaluated in two new trials as part of heterologous vaccine regimens. One, a University of Oxford trial run by the U.K.’s National Immunisation Schedule Evaluation Consortium (NISEC), will assess the feasibility of using different vaccines for the initial vaccination and the booster.

The COVID-19 Heterologous Prime Boost study (informally, the Com-Cov study) will evaluate four different combinations: a first dose of AZD1222 followed by boosting with either Comirnaty from Pfizer Inc. (NYSE:PFE) and BioNTech SE (NASDAQ:BNTX) or a further dose of AZD1222, or a first dose of Comirnaty followed by boosting with either AZD1222 or a further dose of Comirnaty.

The 13-month study plans to enroll more than 800 volunteers aged 50 and up from eight National Institute for Health Research (NIHR) supported sites in England. 

Backed by £7 million ($9.6 million) in funding from the Vaccines Taskforce, the study will employ two different dosing schedules: at a four-week interval for an early interim data readout and at a 12-week interval for comparison to U.K. policy.

The second study is a Phase I/II vaccine combination trial of AZD1222 and Sputnik V from N.F. Gamaleya Scientific Research Institute of Epidemiology and Microbiology that is slated to start next month, according to ClinicalTrials.gov. The trial participants will either receive AZD1222 on day 1 followed by Sputnik V on day 29, or vice versa. The estimated completion date is mid-November.

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