AstraZeneca have announced a clinical trial programme to assess safety and immunogenicity of a combination of AZD1222, developed by AstraZeneca and Oxford University, and Sputnik V, developed by Russian Gamaleya Research institute.
Dr Zoltán Kis, Research Associate at the Future Vaccine Manufacturing Hub, Imperial College London, said:
“Both the AstraZeneca/Oxford vaccine candidate and the Sputnik V vaccine are adenovirus vectored vaccines and both deliver genetic instructions for the cells of the body to produce the Spike protein of SARS-CoV-2. The AstraZeneca/Oxford vaccine candidate is based on a chimpanzee adenovirus and the Sputnik V vaccine is based on a human adenovirus, thus the vectors (or carriers) of these two vaccines are slightly different.
“The immune system of the human body can generate an immune response against the adenoviral vector itself, thus if a second dose of the same adenovirus vectored vaccine is delivered, the immune system could destroy the vector, before the payload of the vaccine is delivered, therefore reducing the efficacy of the second vaccine dose. On the other hand, if the vector of the second (booster) dose of the vaccine is different from the vector of the first (prime) dose, the immune system will be less likely to destroy the vector of the vaccine, thus the efficacy of the heterologous boosting vaccination could be increased, compared to the situation where both the prime and boost doses were of the same vector type. Therefore, the reason why heterologous boosting could increase vaccine efficacy, is that the (partial) destruction of the second vaccine dose by the immune system can be avoided and because both vaccines contain instructions for producing the same antigen.
“Furthermore, having the possibility of combining these two vaccine types would allow for greater flexibility in the vaccination programs. This could lead to greater accessibility to vaccines, thus increasing the rate and scale of Covid-19 vaccination coverage.
“For these reasons, the news regarding clinical trials of this heterologous boosting Covid-19 vaccination is a promising one.”
Prof Helen Fletcher, Professor of Immunology at the London School of Hygiene & Tropical Medicine, a vaccines expert and UKRI’s Director of International Development, said:
“This is the logical next step in vaccine development for COVID-19 as priming with one type of vaccine and boosting with another is a commonly used strategy for increasing the level and duration of efficacy against infectious disease. Combining vaccines has the potential to be more effective through boosting immune responses to a higher level and maintaining immunity over a longer period of time.
“The AZD1222 vaccine given alone would prime an immune response against spike protein – but also prime a response against the vaccine itself – giving AZD1222 a second time increases immune responses against spike protein but this increase is limited because our immune system recognises and neutralises some of the vaccine particles before they can express the spike protein. In a heterologous boost we would give spike protein using one vaccine platform and then present the same spike protein using a different vaccine platform – this could give a much stronger immune response to spike because the second vaccination isn’t limited by any anti-vector immune response.
“Combining AZD1222 with an mRNA vaccine would be a heterologous boost as the vaccine platforms are very different. Combining 2 different adenoviruses could be a heterologous boost if the two viral vectors are different enough to avoid anti-vector immunity. It would make sense in terms of vaccine distribution to use two adenovirus vaccines together so definitely worth testing.”
Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:
“The strategy of heterologous boosting is pertinent to the use of adenovirus-based vaccines. Adenovirus vaccines can become a victim of their own success as they are fairly potent inducers of immunity, so much so that the body often mounts a response to the incoming vehicle, or “vector”, comprising replication-disabled virus particles, in addition to the vaccine payload, or “immunogen” that it delivers. This can mean that using the same vehicle again is less effective as antibodies made as part of this “anti-vector” response can reduce the efficiency of the second jab – the vehicle doesn’t get to deliver its second payload.
“This phenomenon may have been a contributing factor for the patients receiving the higher initial dose of the ChAdOX vaccine, where reduced efficacy was observed. Even though our immune systems haven’t seen the chimpanzee adenovirus before, the first viewing at the higher dose potentially generates sufficient responses to lessen the effect of the second boost. The sputnik vaccine avoids this issue by using two different human adenoviruses for the first and second shot, meaning the anti-vector response is far less likely to have a negative impact. Thus, combinations of these vaccines will give more flexibility in terms of regimens going forwards, and it is also encouraging to hear that combinations of adenovirus and RNA vaccines are planned.
“The importance of a second jab should not be underestimated as it is important for the longevity, specificity and effectiveness of the response to most vaccines.”
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Prof Helen Fletcher: “Director of international development UKRI. Trustee of the Jenner Vaccine Foundation.”
Dr Stephen Griffin: “No conflicts.”
None others received.