ChAdOx1 nCoV-19 vaccine for SARS-CoV-2 – Authors' reply

We agree with Anil Chauhan and colleagues that recording of anaphylaxis is important when testing a new vaccine. All participants in the trial were observed in the clinic for at least 30 min after they were vaccinated, and no cases of anaphylaxis occurred.¹

1067 participants in the trial were randomly assigned (1:1) to receive either ChAdOx1 nCoV-19 or the control meningococcal conjugate vaccine (MenACWY), with an additional ten participants enrolled into a non-randomised subgroup, who all received two doses of the ChAdOx1 nCoV-19 vaccine. There were no additional criteria for the selection of participants for this group, other than their willingness to receive two doses of vaccine and attend additional study visits for blood sampling.

Chauhan and colleagues emphasise the different numbers of participants analysed at different timepoints in figure 3.¹ The variation in numbers is due to the timing of blood sampling for different groups in the trial. Only a subset of participants enrolled in group 1 or group 3 had blood samples taken at days 7, 14, and 56. All participants had baseline and day 28 samples taken but, due to low laboratory capacity, not all samples had been tested at the time of publication and so we reported the data that were available at the time of publication. Further data on immunogenicity will be available in the future.

Receipt of prophylactic paracetamol with the ChAdOx1 nCoV-19 vaccine did not result in higher rates of itching than for participants who did not receive paracetamol with this vaccine, as can be seen in the analysis in figure S2 in the appendix,¹ in which the p value for comparison of itching in partici­pants who received paracetamol and participants who did not was p=0·85.

Chauhan and colleagues are correct that an assessment of vaccine efficacy is not usually a part of a phase 2 trial. The large size of the trial and the inclusion of efficacy as an endpoint emphasise the unusual circumstances in which research into COVID-19 vaccines is being done. These are unprecedented times in vaccine research.

We are pleased to read the Correspondence from Archie Lodge, a participant in the trial, and thank him for his time and commitment to participating in this important research. As Lodge rightly points out, maintaining participant masking in any trial is of great importance, as a participant with knowledge of which vaccine they received might alter their behaviour, such as physical-distancing measures, potentially introducing bias into study findings. For this reason, we selected a control vaccine (MenACWY) that also elicited local and systemic reactions in some participants, although reaction rates were lower than for the ChAdOx1 nCoV-19 vaccine. For any individual, it is difficult for them to know whether the reactions that they had were related to the investigational vaccine or the control vaccine. Although some participants might draw conclusions about the vaccine that they received on the basis of figure 1 of our Article,¹ it is important, and standard practice, that safety data are presented openly in this way. We strongly recommend that all trial volunteers continue to protect themselves and their contacts from the pandemic virus by following public health guidance, as participants cannot identify which trial arm they were assigned to until formal unmasking occurs at the end of the trial.