Comparison of Antibody Persistence up to 6 Months after Additional Booster Vaccination with ChAdOx1 nCoV-19 Vaccine
, Phanupong Phutrakool 4, Chatpol Samuthpongtorn 1,3,4, Wannarat Pongpirul 1, Wisit Prasithsirikul 1 and Krit Pongpirul 2,4,5,*Round 1
Reviewer 1 Report
General comment:
The authors examined sequential antibody titers from 170 health care workers precisely. The data are presented clearly, although descriptive. The present manuscript represents a more limited advance than the previous reports, and the impact of this research is not so significant.
Health care workers are more likely infected with SARS-CoV-2 than non-health care workers (general population). Were there any health care workers who got infected with SARS-CoV-2 during observation period? Check anti-N antibody. The authors should rule out the possibility that the increase in the anti-S antibody titer was derived from the infection with SARS-CoV-2.
Specific points:
Line 62-: Divide Materials and Methods into several sections so that the reader can understand more easily.
Line 62-: In the Materials and Methods section, the name of the company should be described for each material; e.g. test kit (Line 71), the recombinant S1 domain of the spike protein of SARS-CoV-2 (Line 72-73), an enzyme-labeled anti-human IgG (enzyme conjugate) (Line 76) etc.
Lines 92-93: Describe the rational for antibody titers; e.g. provide some references for Negative (< 32) and Positive (≧ 32).
Figs. 2 and 4: Describe the definition of %IH in the relevant section of the text.
Fig. 6: Describe the definition of PVNT50 in the relevant section of the text.
Moderate editing of English language required.
Author Response
Reviewer 1: General comment: The authors examined sequential antibody titers from 170 health care workers precisely. The data are presented clearly, although descriptive. The present manuscript represents a more limited advance than the previous reports, and the impact of this research is not so significant.
Response: Thank you very much for your comments. The present work contributes a relatively modest marginal findings; however, these data are not easily available elsewhere. We have (1) re-analyzed all samples to include an analysis of immune responses at 6 months after the third vaccination; (2) investigated the neutralizing response to variants, which has not been previously explored; (3) provided valuable insights into the stability of immune responses, especially the observation that immune responses remain above the protection threshold between 3 and 6 months after a sharp drop observed from 1 to 3 months. This finding enhances our understanding of the long- term efficacy of vaccines and can inform public health policies.
Reviewer 1: Health care workers are more likely infected with SARS-CoV-2 than non-health care workers (general population). Were there any health care workers who got infected with SARS-CoV-2 during observation period? Check anti-N antibody. The authors should rule out the possibility that the increase in the anti-S antibody titer was derived from the infection with SARS-CoV-2.
Response: As mentioned in the manuscript (Line 125-126), none of the participants had a history of Covid-19 infection.
Reviewer 1: Specific points: Line 62-: Divide Materials and Methods into several sections so that the reader can understand more easily.
Response: The Materials and Methods section was reorganized as advised.
Reviewer 1: Line 62-: In the Materials and Methods section, the name of the company should be described for each material; e.g. test kit (Line 71), the recombinant S1 domain of the spike protein of SARS-CoV-2 (Line 72-73), an enzyme-labeled anti-human IgG (enzyme conjugate) (Line 76) etc.
Response: The name of the company was added as suggested.
Reviewer 1: Lines 92-93: Describe the rational for antibody titers; e.g. provide some references for Negative (< 32) and Positive (≧ 32).
Response: The reference was added as suggested.
Reviewer 1: Figs. 2 and 4: Describe the definition of %IH in the relevant section of the text.
Response: %IH is percent of inhibition of RBD-ACE2 binding measured at different time points. This definition was added to the text as suggested.
Reviewer 1: Fig. 6: Describe the definition of PVNT50 in the relevant section of the text.
Response: The definition of PVNT50 was added to the text as suggested.
Reviewer 2 Report
Authors presented the vaccination trial results, where ChAdOx1 nCoV-19 was used as a third booster following two doses of CoronaVac vaccine (Sinovac Biotech). The data shows that ChAdOx1 nCoV-19 as third booster showed robust immune response in form of sustained antibody responses. The antibody titres were stable for six months following vaccination with ChAdOx1 nCoV-19. The presented data is of interest for the field as well as policy makers.
There are some issues with data presentation that can be improved. The figure titles are minimal at the moment and must be improved to include relevant information. As such, the figures should be stand alone in a way that reader can readily understand the data without reading the manuscript text. Also, data presentation needs to be improved, the outliers (responders with high titre) lead to compressed view of the normal responses. This perhaps can be remedied by using some other form of plots, such as Box and whiskers plots that take the outliers into account or authors should split the y-axis. This way the normal data spread can be appreciated and outliers can also be accommodated.
Author Response
Reviewer 2: Authors presented the vaccination trial results, where ChAdOx1 nCoV-19 was used as a third booster following two doses of CoronaVac vaccine (Sinovac Biotech). The data shows that ChAdOx1 nCoV-19 as third booster showed robust immune response in form of sustained antibody responses. The antibody titres were stable for six months following vaccination with ChAdOx1 nCoV-19. The presented data is of interest for the field as well as policy makers.
Response: Thank you very much. We are pleased to know that our work is beneficial.
Reviewer 2: There are some issues with data presentation that can be improved. The figure titles are minimal at the moment and must be improved to include relevant information. As such, the figures should be stand alone in a way that reader can readily understand the data without reading the manuscript text.
Response: Thank you very much for the suggestions. The figure titles were improved as advised.
Reviewer 2: Also, data presentation needs to be improved, the outliers (responders with high titre) lead to compressed view of the normal responses. This perhaps can be remedied by using some other form of plots, such as Box and whiskers plots that take the outliers into account or authors should split the y-axis. This way the normal data spread can be appreciated and outliers can also be accommodated.
Response: Thank you for your valuable feedback. In response to your suggestion, we implemented box and whisker plots to visualize the median, interquartile range, and potential outliers for each visit. Additionally, we performed non-parametric statistical testing, specifically the Wilcoxon Signed Rank Test, to access the significance of our findings. We found that the results from the statistical analysis aligned with our previous findings, indicating that there were statistically significant differences between every visit. Based on these findings, we believe that the addition of box and whisker plots may not provide substantial benefits beyond what has already been conveyed through the statistical analysis. The existing analysis has successfully captured the differences in responses between visits, reaffirming the robustness of our conclusions.
Reviewer 3 Report
1. These authors have reported prospective study on 170 healthcare workers who received 2 doses of a vaccine and then received a third dose of another vaccine as a booster. IgG antibodies against the spike protein were measured at baseline, then 1 month, then 3 months, and then 6 months following vaccination. In addition, neutralizing antibodies were also measured. Finally neutralizing antibodies against several SARS-CoV- 2 variants were measured at 6 months after boosting.
2. The study demonstrates that the recipients had significant increases in IgG antibody titers and neutralizing antibody titers after booster vaccination. The vaccine had a variable effect against different SARS- CoV-2 variants but did produce protective titers.
3. The authors should provide more detail regarding the types of vaccines used in this study. Have similar study has been published? In addition, they should provide more information about the pseudovirus-based neutralization assays. The nonexpert reader will not likely understand the exact experimental details which allows the investigators to determine neutralizing activity against several different viral variants.
Author Response
Reviewer 3: 1. These authors have reported prospective study on 170 healthcare workers who received 2 doses of a vaccine and then received a third dose of another vaccine as a booster. IgG antibodies against the spike protein were measured at baseline, then 1 month, then 3 months, and then 6 months following vaccination. In addition, neutralizing antibodies were also measured. Finally neutralizing antibodies against several SARS-CoV- 2 variants were measured at 6 months after boosting.
Response: Thank you very much. That is correct.
Reviewer 3: 2. The study demonstrates that the recipients had significant increases in IgG antibody titers and neutralizing antibody titers after booster vaccination. The vaccine had a variable effect against different SARS- CoV-2 variants but did produce protective titers.
Response: That is correct.
Reviewer 3: 3. The authors should provide more detail regarding the types of vaccines used in this study. Have similar study has been published? In addition, they should provide more information about the pseudovirus-based neutralization assays. The nonexpert reader will not likely understand the exact experimental details which allows the investigators to determine neutralizing activity against several different viral variants.
Response: Thank you very much for your comments. Yes, the immunogenicity of ChAdOx1 nCoV-19 booster vaccination was published in 2022 (DOI: 10.3390/vaccines10020217). The study revealed a significant improvement for both humoral and cellular immunity one month after vaccination, but the immunity level declined at three months post-vaccination. Despite the similar population and methodology, we have (1) re-analyzed all samples to include an analysis of immune responses at 6 months after the third vaccination; (2) investigated the neutralizing response to variants, which has not been previously explored; (3) providedvaluable insights into the stability of immune responses, especially the observation that immune responses remain above the protection threshold between 3 and 6 months after a sharp drop observed from 1 to 3 months. This finding enhances our understanding of the long- term efficacy of vaccines and can inform public health policies.
Round 2
Reviewer 1 Report
N/A
