Humoral and Cellular Responses to COVID-19 Vaccines in SARS-CoV-2 Infection-Naïve and -Recovered Korean Individuals
, Jong-Geol Jang 3, June-Hong Ahn 3 and Hosun Park 1,4,*Round 1
Reviewer 1 Report
The manuscript contains the results of important study of parameters of humoral and cellular components of immunity produced by COVID-19 vaccines in infection-naive and -recovered Koran individuals. The current situation of SARS-CoV-2 pandemic is quite complicated because of presence a lot of both vaccinated and recovered individuals and evolution of the pathogen which requires periodic re-vaccinations accompanying with the shortage of vaccines. The manuscript describes the results of application of different combinations of vaccines for infection-naive and - recovered people with the purpose to find a way to diminish the amout of vaccine doses.
The study is professionally planned and organized, all the ethical norms are applied, the conclusion is strongly based on the results obtained and these results may be a good basement for modification of vaccination schedules and vaccination manuals.
The shortage of the study is a limited amount of vaccinees. But it is mentioned by authors themselves.
Author Response
The manuscript contains the results of important study of parameters of humoral and cellular components of immunity produced by COVID-19 vaccines in infection-naive and -recovered Koran individuals. The current situation of SARS-CoV-2 pandemic is quite complicated because of presence a lot of both vaccinated and recovered individuals and evolution of the pathogen which requires periodic re-vaccinations accompanying with the shortage of vaccines. The manuscript describes the results of application of different combinations of vaccines for infection-naive and - recovered people with the purpose to find a way to diminish the amount of vaccine doses.
The study is professionally planned and organized, all the ethical norms are applied, the conclusion is strongly based on the results obtained and these results may be a good basement for modification of vaccination schedules and vaccination manuals.
The shortage of the study is a limited amount of vaccinees. But it is mentioned by authors themselves.
Response: Thank you for your kind review.
Reviewer 2 Report
In this report, the authors studied the immunogenicity of single or double COVID-19 vaccination in SARS-CoV-2-recovered individuals. The authors' data reveal no significant difference in neutralizing antibody and T cell responses between the one- and two-dose regimens nor vaccine type (mRNA vs. adenovirus). The author show that, compared to SARS-CoV-2-naive individuals, a single dose of an adenovirus COVID-19 vaccine (ChAdOX1) was capable of inducing substantial recall humoral and cellular immune responses.
The study described in this manuscript was well devised and conducted. However, the relatively small sample size raises questions as to whether the findings can be extrapolated to the population at large. The results of the study were convincing. However, outside of the ChAdOX1 immunogenicity data from SARS-CoV-2-recovered individuals, the data are not very striking since several other reports have established that a single-dose regimen is sufficient to induce humoral and cellular immunity in recovered individuals.
My major comments have to do with the Conclusions section:
1. I feel that the data are supportive enough that the authors should highlight the potential benefits of ChAdOX-1 vaccination in individuals with a history of lab-diagnosed SARS-CoV-2 infection (i.e., cost, thermostability, scalability).
2. Also, do the authors intend to perform a follow-up study on durability of responses in SARS-CoV-2-recovered individuals? Though the initial data suggest that mRNA and adenovirus vaccines possess comparable abilities to elicit humoral and cellular immunity, it would be important to understand the kinetics of neutralizing antibody titers in the experimental groups (Figure 2, Table 3) in light of data suggesting that protection following mRNA-1273 vaccination lasts longer that that following BNT162b2 vaccination.
I also have a comment about the study group. It's unclear to me when individuals in YUMC-COVID-R02 study group were initially diagnosed as SARS-CoV-2-infected. This is important for understanding whether individuals were infected with the same viral variant. This has implications for the antibody data. All individuals appear to mount neutralizing antibody responses against the spike protein from the original Wuhan strain (Addgene #145032). It would be interested to study whether the humoral responses elicited in vaccinated-recovered individuals possessed neutralizing ability against more recent variants (i.e., Beta, Delta, and Omicron).
Author Response
My major comments have to do with the Conclusions section:
- I feel that the data are supportive enough that the authors should highlight the potential benefits of ChAdOX-1 vaccination in individuals with a history of lab-diagnosed SARS-CoV-2 infection (i.e., cost, thermostability, scalability).
Response: Thank you for your comments. As suggested, we have added texts to describe some benefits of ChAdOX-1 vaccine such as temperature stability and low cost.
Line 330-332: Because ChAdOX1 have several benefits, such as low cost and refrigerating temperature stability, it would be beneficial to administrate ChAdOX1 vaccine for the SARS-CoV-2-recovered individuals in tropical areas or low income countries.
- Also, do the authors intend to perform a follow-up study on durability of responses in SARS-CoV-2-recovered individuals? Though the initial data suggest that mRNA and adenovirus vaccines possess comparable abilities to elicit humoral and cellular immunity, it would be important to understand the kinetics of neutralizing antibody titers in the experimental groups (Figure 2, Table 3) in light of data suggesting that protection following mRNA-1273 vaccination lasts longer that that following BNT162b2 vaccination.
Response: Thank you for your question and comments. Yes, we have a plan to follow up the immune response of SARS-CoV-2 recovered individuals until 36 months post initial symptom onset. Now, many of the subjects were vaccinated and we will follow-up their immunity and will compare the difference according to the vaccine type in the future.
I also have a comment about the study group. It's unclear to me when individuals in YUMC-COVID-R02 study group were initially diagnosed as SARS-CoV-2-infected. This is important for understanding whether individuals were infected with the same viral variant. This has implications for the antibody data. All individuals appear to mount neutralizing antibody responses against the spike protein from the original Wuhan strain (Addgene #145032). It would be interested to study whether the humoral responses elicited in vaccinated-recovered individuals possessed neutralizing ability against more recent variants (i.e., Beta, Delta, and Omicron).
Response: Thank you for your comments. All of the subjects of YUMC-COVID-R02 study group had diagnosed during first wave outbreak in Daegu (from February 2020 and April 2020). Therefore, most of the subjects were considered be infected with S and V clade of wild type SARS-CoV-2 (Reference 19). Indeed, we have a plan to analyze neutralizing antibody titers against Delta and Omicron variants using sera from YUMC-COVID-R02 study group subjects for further study.
As suggested, we have added the information of diagnosis period in the section describing the subjects of YUMC-COVID-R02 study group. And also added the reference of prevalent SARS-CoV-2 type during that period in Korea.
Line 79-80: COVID-19-convalescent patients had been diagnosed with RT-PCR during first wave of COVID-19 (from February 2020 to April 2020)[19].
Author Response File: 
Author Response.docx
