key: cord-0724715-vyyzcjlp
authors: Sasikala, Mitnala; Shashidhar, Jaggaiahgari; Deepika, Gujjarlapudi; Ravikanth, Vishnubhotla; Krishna, Vemula Venkata; Sadhana, Yelamanchili; Pragathi, Kottapalli; Reddy, Duvvur Nageshwar
title: Immunological memory and neutralizing activity to a single dose of COVID-19 vaccine in previously infected individuals
date: 2021-05-19
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2021.05.034
sha: c2149e54b0c63d7292c3e77e470deb1ee643db15
doc_id: 724715
cord_uid: vyyzcjlp

BACKGROUND: Individuals who have recovered from SARS-CoV-2 infection were shown to have higher antibody response to a single dose of mRNA vaccines while memory response was demonstrated in COVID-19 patients up to 8 months. The efficacy of vaccines to generate immunological memory post vaccination has not been studied. OBJECTIVE: To assess immunological memory in previously infected individuals after a single dose of vector based vaccine PATIENTS AND METHODS: Healthcare workers (n = 280) were enrolled after obtaining written informed consent and grouped under previously infected (RT-PCR positive) and no prior exposure group (RT-PCR negative). Blood was drawn at baseline and post vaccination (single dose of COVISHIELD) for enumerating neutralizing antibodies by Chemiluminiscence and memory T and B cells employing flow cytometry. RESULTS: A higher antibody response (1124.73 ± 869.13 vs94.23 ± 140.06 AU/ml; p = 0.0001), CD4 memory T-cells; central memory CCR7+CD45RA- (p = 0.0001), effector memory CCR7-/CD45RA- (0.01), total CD8+T cells; (p = 0.004), CD8+naïve T cells CCR7+CD45RA+; (p = 0.01) and memory B cells CD20+CD27+; (p = 0.0001) was seen in previously infected individuals with a single dose of vaccine. DISCUSSION: Single dose vaccination elicited higher neutralizing antibody response and protective immunity in individuals who were previously infected. Hence single dose strategy may be pursued to increase population coverage.

 Vaccine elicited immune response in majority of the individuals  Previously infected individuals showed higher neutralizing antibody response  Higher memory cell response seen in previously infected individuals  Single dose vaccination in previously exposed individuals is an efficient strategy  Such a strategy enables larger population coverage Abstract Background Individuals who have recovered from SARS-CoV-2 infection were shown to have higher antibody response to a single dose of mRNA vaccines while memory response was demonstrated in COVID-19 patients up to 8 months. The efficacy of vaccines to generate immunological memory post vaccination has not been studied.

To assess immunological memory in previously infected individuals after a single dose of vector based vaccine

Healthcare workers (n=280) were enrolled after obtaining written informed consent and grouped under previously infected (RT-PCR positive) and no prior exposure group (RT-PCR negative). Blood was drawn at baseline and post vaccination (single dose of COVISHIELD) for enumerating neutralizing antibodies by Chemiluminiscence and memory T and B cells employing flow cytometry.

A higher antibody response (1124.73±869.13 vs94.23±140.06 AU/ml; p=0.0001), CD4 memory T-cells; central memory CCR7+CD45RA-(p=0.0001), effector memory CCR7-/CD45RA-(0.01), total CD8+T cells; (p=0.004), CD8+naïve T cells CCR7+CD45RA+; J o u r n a l P r e -p r o o f (p=0.01) and memory B cells CD20+CD27+; (p=0.0001) was seen in previously infected individuals with a single dose of vaccine.

Single dose vaccination elicited higher neutralizing antibody response and protective immunity in individuals who were previously infected. Hence single dose strategy may be pursued to increase population coverage.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has resulted in unprecedented mortality and morbidity globally. In the absence of specific therapeutic drugs to treat COVID-19, vaccines are currently the only alternative option in the control of SARS-CoV-2 infection (Krammer F, 2020) . COVID-19 vaccination programs initiated worldwide resulted in decreased disease severity (Rinott E et al., 2020) . Vaccinating huge populations need evidence based strategies for successful implementation and control of the pandemic.

Although individuals who have had COVID-19 were shown to have higher antibody response to a single dose of mRNA vaccine, (Krammer F et al., 2021 , Saadat S et al., 2021 their efficacy to generate immunological memory and protection against reinfection of SARS-CoV-2 is not yet reported. If a single dose could induce adequate immunological memory in previously infected individuals in addition to higher neutralizing activity, the available doses can be used for vaccinating and protecting larger number of additional populations. Therefore, our aim was to assess immunological memory in previously infected individuals after a single dose of vector based vaccine.

We enrolled healthcare workers (n=280) who were vaccinated between 16 th January and 5 th February 2021 at AIG hospitals, Hyderabad, India (a hospital recognized by Indian council of Medical research to test, treat and vaccinate individuals) for assessing immunological memory response. Participants who were earlier RT-PCR positive for SARS-CoV-2 and recovered formed the previously infected group and participants who were RT-PCR negative formed no prior exposure group. All the participants were given COVISHIELD (AstraZeneca vaccine ChAdOx1/AZD1222 manufactured by Serum Institute of India) in two doses, 28 days apart as per the then guidelines. Side effects after the single dose of vaccine were noted for all the participants. Blood was drawn at days 0 (base line) and 28 (post single dose) from all the participants. Serum samples were tested for neutralizing antibodies (IgG) employing Chemiluminiscence (Shang W et al., 2020) and day 28 samples were analyzed for neutralizing antibodies and memory cells by flow cytometry (Qianting Yang et al., 2020) .

The study was approved by institutional ethics committee and all the participants provided written informed consent. Students t test and Z proportion test were used to test differences between the groups. A p-value of <0.05 was considered significant.

Participant demographics, base line sero-status and frequency of side effects after single dose of vaccination are given (Table 1) . Of the 280 individuals enrolled in the study,131 were RT-PCR positive with mild to moderate disease, 50 of them requiring hospital admission. All 131 (46.78%) were seropositive and 149 (53.22%) were seronegative prior to first dose of vaccination.

Base line neutralizing antibodies were significantly higher in previously infected individuals as compared to no prior exposure group (61.58±46.88 vs 5.03±2.54 AU/ml p=0.0001). All J o u r n a l P r e -p r o o f the seropositive (100%, n=131) and 94.6% (n=141) seronegative participants developed neutralizing antibodies by day 28 after the first dose of COVISHIELD. Previously infected individuals mounted greater antibody response (1124.73±869.13 vs94.23±140.06 AU/ml; p=0.0001) to single dose of COVISHIELD vaccine compared to those not infected ( Figure   1 ).

Memory 

Our results demonstrate that individuals who were previously infected mounted higher immune and memory responses to a single dose of vector based vaccine compared to those with no prior exposure. Earlier studies reported immune memory to SARS-CoV-2 infection (Rodda LB et al., 2021 , Dan JM et al., 2021 and higher antibody response with single dose J o u r n a l P r e -p r o o f 6 in previously infected individuals (Rinott E et al., 2021) . Our study reports higher Memory T and B cell responses in addition to higher antibody response with single dose of COVISHIELD given at 3-6 months after recovery from COVID-19. These results suggest protective immune memory in previously exposed individuals after single dose of vaccine.

Such individuals could mount memory recall response on subsequent encounter with antigen as they developed adaptive immune memory. Thus, individuals who have had COVID-19 and recovered would have adequate protection even with single dose of vaccine. Our results demonstrate evidence to support single dose vaccination strategy for previously infected individuals to increase coverage and protect larger number of populations. However, all the non-infected individuals are required to compulsorily take the second dose of vaccine. In addition, longitudinal follow up studies are required to assess the longevity of protective memory/ to arrive at timing of second dose.

The study was approved by Institutional Ethics Committee of AIG Hospitals, Hyderabad, India.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. J o u r n a l P r e -p r o o f Panel A shows antibody titers against S1 and S2 sub units of spike protein of SARS-CoV-2 with single dose of COVISHIELD in individuals previously exposed and in individuals with no prior exposure. Antibody titers were significantly higher (p<0.0001) in previously exposed individuals (1124.73± 869.13AU/ml) as compared to no prior exposed individuals (61.58±46.88 AU/ml).

Panel B Shows memory T cell response after a single dose of SARS-CoV-2 vaccine, COVISHIELD (n=50 individuals with previous infection and 50 with no prior exposure).

Significantly higher memory T cell response is elicited by a single dose in previously exposed individuals than in those who were not exposed: Central memory cells Panel C shows memory B cell response after a single dose of SARS-CoV-2 vaccine, COVISHIELD. Significantly higher memory B cell response is elicited by single dose in previously exposed individuals than those who were not exposed: Total B cells (CD45+CD20+ p=0.0005), memory B cells (CD20+CD27+ P=0.0001) and activated B cells (CD45+HLADR+p=0.0001). 

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