Immunogenicity and efficacy of heterologous ChadOx1/BNT162b2 vaccination amongst healthcare staff

Extreme antagonistic reactions have been reported after the AstraZeneca ChAdOx1-S-nCoV-19 vaccine (ChAd). This prompted the European well being authorities to suggest the popular second dose to be Pfizer BNT162b2 vaccine (BNT) as a booster for sufferers beneath 55 who obtained the primary dose of ChAd.

Study: Immunogenicity and efficacy of heterologous ChadOx1/BNT162b2 vaccination. Image Credit: AlessandroBiascioli/ ShutterstockResearch: Immunogenicity and efficacy of heterologous ChadOx1/BNT162b2 vaccination. Picture Credit score: AlessandroBiascioli/ Shutterstock

A brand new examine revealed in Nature revealed that the heterologous ChAd/BNT mixture (as the primary and second doses) confers higher safety towards extreme acute respiratory syndrome coronavirus-2 (SARS-CoV-2) an infection than the homologous BNT/BNT mixture in a real-world observational examine of healthcare staff (HCWs).

The examine

This examine entailed a longitudinal survey together with 13,121 HCWs; the anti-spike immunity conferred by every vaccine mixture was assessed. Right here, knowledge was extracted from the occupational drugs database of the College hospital of Lyon (Hospices Civils de Lyon, HCL), France.

It was famous that ten infections occurred amongst 2,512 people within the heterologous vaccination group, in comparison with 81 infections amongst 10,609 within the homologous vaccination group. The outcomes depicted that each vaccine mixtures induced robust anti-spike antibody (Ab) responses. Nevertheless, sera from heterologous vaccinated people displayed a stronger neutralizing exercise, whatever the causative SARS-CoV-2 variant.

It was famous that this enhanced neutralizing potential was in keeping with elevated frequencies of switched and activated reminiscence B cells recognizing the SARS-CoV-2 Receptor Binding Area (RBD). In the meantime, ChAd induced a weaker IgG response however a stronger T cell response than the BNT after the primary dose. Thus, the heterologous vaccination routine could also be appropriate for immunocompromised people.

A number of logistic regression mannequin analyses revealed that age was not related to the chance of buying an infection. Whereas the likelihood of being contaminated after vaccination considerably depended upon the vaccination routine. It was discovered that people who obtained BNT/BNT have been twice as prone to be contaminated as those that got ChAd/BNT.

Moreover, the flexibility of serum samples to neutralize SARS-CoV-2 spike-pseudotyped viral particles was measured. The findings indicated neither of the sera displayed neutralizing exercise earlier than vaccination or after the primary dose. In the meantime, most elicited a neutralizing exercise after the second dose; sera from the ChAd/BNT vaccinated sufferers displayed the next neutralizing efficacy than these from the BNT/BNT vaccinated people.

The power of the sera to stop VeroE6 cell an infection by SARS-CoV-2 isolates belonging to varied Clades was examined. The ChAd/BNT vaccinated people exhibited 2.3-fold-to-3.6 greater serum neutralizing Ab titers towards the completely different variants than people from the BNT/BNT group. These findings advised that the neutralizing potential of Abs generated by heterologous vaccination is much less affected by spike mutations showing in Variants of Concern (VOCs) than that of Abs induced by homologous vaccination.

As well as, the T-cell response of vaccinees towards RBD peptides was longitudinally monitored, utilizing an entire blood interferon (IFN) γ launch assay. The outcomes confirmed that the T cell response was greater after ChAd immunization than after BNT priming and was equally elevated by BNT enhance. Each vaccination regimens might set off a progressive improve within the frequency of S-reactive CD4 and CD8 T cells from the pre-vaccine to the post-booster part.         Furthermore, the heterologous mixture resulted in a stronger CD4 T cell response, each after the first dose and the booster, and an rising development of the CD8 T cell response after the booster dose.

Moreover, the neutralizing Ab exercise was related to the S1 or RBD-specific IgG titers, regardless of the variant analyzed and was not related to IgA ranges. These outcomes indicated that higher neutralizing Abs are produced from sustained B cell activation. Therefore, the Abs high quality underlies the superior neutralization potential of the Abs response induced by heterologous vaccination.

As well as, one examine in contrast vaccination schedules with the identical prime-boost interval. The findings confirmed that for brief intervals, the humoral responses induced by each regimens have been comparable. On the identical time, an extended interval between the 2 doses might facilitate the synergy between heterologous vaccines.


The outcomes of this examine offered a real-world observational delineation of the heterologous ChAd/BNT routine in HCWs. The outcomes confirmed that such modification confers stronger protecting immunity than the homologous BNT/BNT prime-boost schedule. But confirmatory research and an extended follow-up are beneficial to ascertain the above findings and refute confounding components, for example – completely different ranges of publicity to the virus amongst topics.

The findings herein advised that the heterologous ChAd/BNT mixture may very well be significantly appropriate for immune-compromised sufferers.

Journal reference:

  • Pozzetto, B., et al. “Immunogenicity and efficacy of heterologous ChadOx1/BNT162b2 vaccination”, Nature (2021), doi: 10.1038/s41586-021-04120-y

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