Immune responses to a single dose of the AZD1222/Covishield vaccine in health care workers

Several COVID-19 vaccines have received emergency approval. Here we assess the immunogenicity of a single dose of the AZD1222 vaccine, at one month, in a cohort of health care workers (HCWs) (629 naïve and 26 previously infected). 93.4% of naïve HCWs seroconverted, irrespective of age and gender. Haemagglutination test for antibodies to the receptor binding domain (RBD), surrogate neutralization assay (sVNT) and ex vivo IFNγ ELISpot assays were carried out in a sub-cohort. ACE2 blocking antibodies (measured by sVNT) were detected in 67/69 (97.1%) of naïve HCWs. Antibody levels to the RBD of the wild-type virus were higher than to RBD of B.1.1.7, and titres to B.1.351 were very low. Ex vivo T cell responses were observed in 30.8% to 61.7% in naïve HCWs. Previously infected HCWs, developed significantly higher (p < 0.0001) ACE2 blocking antibodies and antibodies to the RBD for the variants B.1.1.7 and B.1.351. This study shows high seroconversion after one vaccine dose, but also suggests that one vaccine dose may be insufficient to protect against emerging variants.

In this manuscript, Jeewandara et al. evaluated the immunogenicity of the AZD1222 vaccine (by AstraZeneca) in a large cohort of health care workers in Sri Lanka. The cohort included individuals with different immune status (naïve or previously exposed to . The authors assessed the seroconversion at early time point (30 days after vaccination), the antibody response (antibody titers to the RBD and neutralization) and the cellular immunity to the Spike protein after a single dose of AZD1222 vaccine. They showed that a single dose of vaccine was able to elicit SARS-COV2 antibody responses targeting the RBD of the virus, which could be associated with protection after 28 days independently of the immune status, moreover pre-exposed covid-19 individuals showed significantly higher immunogenicity compared to naïve individuals. Overall, the authors addressed an important question about the immunogenicity of a single dose vaccination regimen as many countries would have a partially immunized population with different immune status to Covid-19. It is crucial to provide data on immunity to one vaccine dose as well as to study vaccinees with prior SARS-COV2 who were not widely included in efficacy trials. As many variants surge it is important to know the immunogenicity of a vaccine against those variants. The authors should clarify and add more information to improve the manuscript.
The cohort of health care workers used by the authors is not well characterized, some details are missing in table 1. The authors should add more information, for example about the % of female/male per age group, median of months from previous SARS-COV2 infection to vaccination. How was the immune status of pre-exposed individuals was determined? More details are needed about the disease in that group of individuals: % of symptomatic/ Asymptomatic/ hospitalizations/ mild illness/severe. How the pre-immunity is defined? Antibody titers? How is the comorbidity defined in this study (L300)? Please specify.
Due to the number of participants in the study, parametric tests could be more accurate and could give greater statistical power. Please check with statisticians if the statistical tests used in the study are accurate. Line 139: The authors used 69 individuals who were SARS-COV2 negative to measure the HAT titers, how was this cohort of 69 individuals selected? Was the selection random? More details about those individuals should be added. The selection of these individuals could have an impact on the results. Similarly, the reader needs more details about the cohort of 76 individuals used for the T cell response. How was the selection done? Figure 3A: Is there any significant difference in the sVNT titers between the group of naïve and infected individuals after vaccination? In figure 3, the authors presented the sVNT titers (percentage of inhibition of ACE2 binding) against WT virus as a measurement of neutralization. To strengthen the manuscript, the authors should assess the "neutralizing" activity of vaccinees against the variants (B.1.1.7 and B.1.351 as done for the HAT titers. Any correlation between the HAT titers and the sVNT titers for the variants?  Line 272-278: The authors compared the immunogenicity of AZD1222 and BNT162b2 vaccines, although these data are from two different studies. The comparison is not accurate and the authors should revise the discussion about that point. Typos: L135: Delete "s" L156-161: Mention "figure 2 B", this section is confusing without referencing the figures. Reviewer #2: Remarks to the Author: The manuscript by Jeewandara and colleagues describe the immunity of the AstraZeneca Covidshield vaccine in cohort of health care workers. The authors use a combination of antibody and T cell assays to establish broad seroconversion and the elicitation of a degree of T cell immunity after a single dose. Some of the methods are written a little unclearly, as is the description of the results. The question of the utility of single dose immunisation from a public health standpoint is of interest to inform vaccine rollouts. However we already know a single dose of many of the vaccines is immunogenic from phase I studies and others (and even protective in some epidemiological assessments). Ultimately the results presented here are largely confirmatory and the manuscript might be better suited for a more specialised immunology journal. I have some comments below:

Reviewer 1
In this manuscript, Jeewandara et al. evaluated the immunogenicity of the AZD1222 vaccine (by AstraZeneca) in a large cohort of health care workers in Sri Lanka. The cohort included individuals with different immune status (naïve or previously exposed to . The authors assessed the seroconversion at early time point (30 days after vaccination), the antibody response (antibody titers to the RBD and neutralization) and the cellular immunity to the Spike protein after a single dose of AZD1222 vaccine. They showed that a single dose of vaccine was able to elicit SARS-COV2 antibody responses targeting the RBD of the virus, which could be associated with protection after 28 days independently of the immune status, moreover pre-exposed covid-19 individuals showed significantly higher immunogenicity compared to naïve individuals. Overall, the authors addressed an important question about the immunogenicity of a single dose vaccination regimen as many countries would have a partially immunized population with different immune status to Covid-19. It is crucial to provide data on immunity to one vaccine dose as well as to study vaccinees with prior SARS-COV2 who were not widely included in efficacy trials. As many variants surge it is important to know the immunogenicity of a vaccine against those variants. The authors should clarify and add more information to improve the manuscript.
Response: thank you for these positive comments.  Table 1. None of the 26 individuals had severe illness, but 6 had mild, symptomatic illness.
The other 20 individuals were only found to be infected by the detection of SARS-CoV-2 specific antibodies by the antibody assays. This information is included in the revised Results section of the manuscript. comparison is not accurate and the authors should revise the discussion about that point.
Response: Thank you for this very valid comment. We have changed the discussion mentioning that these are from two different studies, although the peptides that were used were from the same source and the same technique/protocol was used. Response: Thank you for these comments. We have corrected these typos.

Reviewer #2 (Remarks to the Author):
The manuscript by Jeewandara and colleagues describe the immunity of the AstraZeneca Covidshield vaccine in cohort of health care workers. The authors use a combination of antibody and T cell assays to establish broad seroconversion and the elicitation of a degree of T cell immunity after a single dose. Some of the methods are written a little unclearly, as is the description of the results. The question of the utility of single dose immunisation from a public health standpoint is of interest to inform vaccine rollouts. However we already know a single dose of many of the vaccines is immunogenic from phase I studies and others (and even protective in some epidemiological assessments). Ultimately the results presented here are largely confirmatory and the manuscript might be better suited for a more specialised immunology journal. I have some comments below: Response: thank you for these positive comments. Table 1 appears incorrect or incomplete. There is no provision of relevant demographic data nor baseline seropositivity data for the cohort that were immunized.

Response:
We thank the reviewer for this comment. We have included demographic data such as the number of males and females in each age group. In addition, table 1, includes the seroconversion rates of the health care workers who were seronegative at baseline. We have also added more information regarding those who were seropositive at baseline and regarding comorbid illnesses in the study participants, in the revised version of Table 1