Mix-and-match COVID-19 vaccines: New trial to add to growing body of research

By Rachel Arthur

- Last updated on GMT


Related tags COVID-19 vaccine COVID-19 vaccine booster

A new clinical trial of heterologous – or ‘mix-and-match’ – combinations of COVID-19 vaccines is set to start in Pakistan: seeking to add to research on the effectiveness of such combinations.

Announced this week, the trial will be run by an international consortium led by Aga Khan University and comprising the National Institute of Health in Pakistan; University of Oxford; the International Vaccine Institute and Harvard Medical School. The Coalition for Epidemic Preparedness Innovations (CEPI) will provide up to $11.7m of funding for the project.

Heterologous combinations of COVID-19 vaccines could help with supply, plugging a gap if a certain vaccine is not available and allowing vaccination campaigns to continue seamlessly. It could also potentially increase vaccine efficacy, particularly if a second vaccine type is more effective against an emerging variant.

Pakistan trial: AstraZeneca, Sinopharm and CanSinoBIO

In Pakistan, the clinical trial will assess the safety and immunogenicity of mix-and-match combinations of three vaccines that are currently available in Pakistan: developed by AstraZeneca, Sinopharm and CanSinoBIO.

“Data on mix-and-match combinations of these vaccines, which are commonly used in low- and middle-income countries (LMICs), are urgently needed to contribute to the design of more flexible vaccination strategies and mitigate against shortages of vaccine at times of uncertain or fluctuating supplies,” ​notes CEPI.

“The trial will also generate valuable data on the immune response after vaccination to the different variants circulating in Pakistan. All of the data will be made available open source to inform policy makers and regulatory authorities’ recommendations on the use of COVID-19 vaccines.”

The Phase 2 clinical trial will be conducted at established trial sites in the cities of Karachi, Lahore and Islamabad, Pakistan. Over 1,600 participants aged 18 years and over will be enrolled into the trial and randomized to receive either a homologous vaccine regimen (two doses of the same vaccine) or a mix-and-match combination of vaccines. All of the possible combinations of the three vaccines will be evaluated in the study.

Trial participants will be followed up for two years to gather important data about the durability of immune responses and the impact of possible booster doses. The first interim results are expected to be available in the first quarter of 2022.

University of Oxford trial shows 'robust immune responses'

Meanwhile, a trial led by the University of Oxford is researching mix-and-match vaccines in the UK in the Com-COV: with data so far suggesting the practice can generate robust immune responses.

The trial started with Pfizer/BioNTech and AstraZeneca vaccines. In June, researchers reported that this combination induced high concentrations of antibodies against the SARS-CoV2 spike IgG protein​ when doses were administered four weeks apart.

In April, the researchers expanded the program to include the Moderna and Novavax vaccines​. And in September, it was further expanded to include 12-16 year olds​ with Pfizer/BioNTech, Moderna and Novavax vaccines.   

Booster doses

The UK is now administering Pfizer and Moderna as a booster dose, even to people initially vaccinated with a different authorized vaccine, following advice issued by the government's Joint Committee on Vaccination and Immunisation (JCVI) in September.  

“After reviewing data on booster responses from different combinations of COVID-19 vaccines, JCVI advises a preference for the Pfizer-BioNTech (BNT162b2/ Comirnaty) vaccine to be offered as the third booster dose irrespective of which product was used in the primary schedule,”​ notes its advice​. “There is good evidence that the Pfizer-BioNTech vaccine is well tolerated as a third dose and will provide a strong booster response.

“Alternatively, individuals may be offered a half dose (50µg) of the Moderna (mRNA-1273/Spikevax) vaccine, which should be well tolerated and is also likely to provide a strong booster response.

“Where mRNA vaccines cannot be offered e.g. due to contraindication, vaccination with the AstraZeneca (ChAdOx1-S/Vaxzevria®) vaccine may be considered for those who received this vaccine in the primary course.”

Azerbaijan study: AstraZeneca and Sputnik

In September, R-Pharm Group, the Russian Direct Investment Fund, and AstraZeneca announced the preliminary results for its study in Azerbaijan on the combined use of the AstraZeneca vaccine with the Sputnik vaccine.​  

Data was collected from the first 20 participants of the study, who had received both components of the combination with AstraZeneca vaccine as the first component and Sputnik Light as the second one administered 29 days later. According to the results of the interim analysis, a fourfold or higher increase in neutralizing antibodies to the spike protein (S-protein) of the SARS-CoV-2 was found in 85% of the volunteers on the 57th day of the study.

The Sputnik vaccine itself is already based on a heterogeneous approach: with the vaccine using human adenovirus serotype 26 in the first dose and human adenovirus serotype 5 in the second dose. The idea is that this allows for a stronger and longer-term immune response compared to vaccines using the same vector for two shots (Sputnik Light is a one-dose version using serotype 26).

Related topics Bio Developments COVID-19

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