Binding and Neutralization Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2 | Vaccination | JAMA | JAMA Network
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Figure.  Anti–SARS-CoV-2 Antibody Responses After a Single Dose of Vaccine in Health Care Workers
Anti–SARS-CoV-2 Antibody Responses After a Single Dose of Vaccine in Health Care Workers

After COVID-19 vaccination, plasma was drawn at 0, 7, and 14 days; IgG binding titers against spike trimer were measured by enzyme-linked immunosorbent assay and live virus neutralization was assessed at days 0 and 14. A, IgG spike trimer half-maximal titers. By 7 days and continuing through 14 days following vaccination, both groups of health care workers with prior infection (asymptomatic and symptomatic) who received a single vaccine dose developed higher peak IgG titers than the antibody (Ab)-negative group. B, Live virus neutralization ID99 (the 99% inhibitory dose, the dilution at which 99% of cells were protected). At 14 days, both groups of health care workers with prior infection (asymptomatic and symptomatic) who received a single vaccine dose developed higher neutralization titers than the Ab-negative group. Horizontal black lines represent median values.

Table.  Study Population Baseline Characteristics
Study Population Baseline Characteristics
1.
Winter  L. US officials debate efficacy of half doses of COVID-19 vaccine. The Scientist. Published January 5, 2021. Accessed February 13, 2021. https://www.the-scientist.com/news-opinion/us-officials-debate-efficacy-of-half-doses-of-covid-19-vaccine-68316
2.
Dan  JM, Mateus  J, Kato  Y,  et al.  Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.   Science. 2021;371(6529):eabf4063. doi:10.1126/science.abf4063PubMedGoogle Scholar
3.
Mullins  KE, Merrill  V, Ward  M,  et al.  Validation of COVID-19 serologic tests and large scale screening of asymptomatic healthcare workers.   Clin Biochem. 2021;S0009-9120(21)00005-9.PubMedGoogle Scholar
4.
Rikhtegaran Tehrani  Z, Saadat  S, Saleh  E,  et al.  Performance of nucleocapsid and spike-based SARS-CoV-2 serologic assays.   PLoS One. 2020;15(11):e0237828. doi:10.1371/journal.pone.0237828PubMedGoogle Scholar
5.
Keech  C, Albert  G, Cho  I,  et al.  Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine.   N Engl J Med. 2020;383(24):2320-2332. doi:10.1056/NEJMoa2026920PubMedGoogle ScholarCrossref
6.
Haute Autorité de Santé (HAS). Stratégie de vaccination contre le SARS-CoV-2: vaccination des personnes ayant un antécédent de Covid-19 [SARS-CoV-2 vaccination strategy: vaccination of people with a history of Covid-19]. Published February 11, 2021. Accessed February 13, 2021. https://www.has-sante.fr/upload/docs/application/pdf/2021-02/strategie_de_vaccination_contre_le_sars-cov-2___vaccination_des_personnes_ayant_un_antecedent_de_covid-19_-_synthese.pdf
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    3 Comments for this article
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    More Open Questions on Vaccination of Health Care Workers Previously Infected With SARS-CoV-2
    Raffaele Pezzilli, MD | Potenza County Medical Association, Italy
    I read with interest the letter published online first in JAMA on  March 1, 2021 by Saman Saadat and coworkers (doi:10.1001/jama.2021.3341). This work adds more insight into how to prevent SARS-CoV-2 infection in symptomatic or asymptomatic health care workers previously infected by this virus. However, some additional data would be useful to report:

    1. Whether the interval time between infection and vaccine administration in symptomatic patients may affect the reported results on binding and neutralization antibody titers.
    2. Whether the type of vaccines administered (Moderna vs Pfizer) may affect in any way the binding and neutralization antibody titers.
    3.
    We need to have results at 12 months to evaluate the persistence of these antibody titers.

    Finally, in my opinion, two questions remain open:

    a) whether the same results can be obtained with the AstraZeneca vaccine and with the one-shot Janssen vaccine recently approved by the FDA and both based on different techniques respecting mRNA vaccines and
    b) the effect of these two vaccines on binding and neutralization antibody titers.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Antibody Titers After a Single Vaccine Dose
    Viroj Wiwanitkit, MD | Dr DY Patil University, Pune, India
    The report by Saadatt et al. provides interesting new knowledge on the antibody response to the new COVID-19 vaccination. Indeed, there are many factors determining the response. The different types of vaccines might induce different antibody responses. The mRNA vaccine might induce only spike protein antibodies whereas the non-mRNA vaccine might induce both nucleocapsid and spike protein antibodies.
    The present report shows the response level in subjects with different backgrounds. Giving a new vaccine that still has no long-term data on safety to a person who might not require it (such as with confirmed previous infection) might be an ethical
    dilemma.


    References

    1. Saadat S, Tehrani ZR, Logue J, et al. Binding and Neutralization Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2. JAMA Published online March 1, 2021. doi:10.1001/jama.2021.3341
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Unfortunate the study was so small, but it informs us...
    George Bekmezian, BS in CS | rationalnuggets.com - researcher
    This study's results imply something many have been advocating for from the onset of the vaccine. If we want to maximize the distribution of the vaccine, let's focus on segments of the population who do not already have antibodies to COVID-19.

    The default position should not have been to vaccinate anyone who meets age and comorbidity thresholds. Instead, those who have already presented a healthy immune response should wait until a) we have more information about the long term effects of the available vaccines and b) they are at least 8 months past their previous COVID-19 infection.

    Some
    may argue that it's possible that there is a subset of the population who may get COVID-19 and recover, but never develop antibodies. This may turn out to be true, but we have no evidence to support the idea that these same people will develop antibodies in response to a vaccine.

    I hope this study can be repeated with a larger sample size. I also hope that the participants of this study will be monitored to better understand the long term ramifications of vaccinating those who already have had an immune response to SARS-COV-2.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Research Letter
    March 1, 2021

    Binding and Neutralization Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2

    Author Affiliations
    • 1Institute of Human Virology, University of Maryland School of Medicine, Baltimore
    • 2Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore
    • 3Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore
    JAMA. 2021;325(14):1467-1469. doi:10.1001/jama.2021.3341

    Current shortages in COVID-19 vaccine production and distribution have led some experts to suggest untested regimens.1 Persons who have had COVID-19 are thought to have protective immunity and memory responses2 for at least 6 months; however, neither recall responses nor ideal vaccine dosing regimens have been studied in those previously infected with SARS-CoV-2. We assessed whether health care workers with previous COVID-19 infection could mount recall responses to a single dose of an mRNA-based COVID-19 vaccine.

    Methods

    Health care workers who had previously enrolled in a hospital-wide serosurvey study,3 conducted from July to August 2020 at the University of Maryland Medical Center, were randomly contacted based on stratification into 3 groups: SARS-CoV-2 IgG antibody–negative (Ab-negative); IgG-positive asymptomatic COVID-19 (asymptomatic); and IgG-positive with history of symptomatic COVID-19 (symptomatic). Participants were vaccinated with either the Pfizer-BioNTech or Moderna vaccine, depending on personal preference and availability. Blood was drawn at days 0 (baseline), 7, and 14 postvaccination in December 2020 and January 2021 (draws could be within 1 day from assigned day). Plasma was tested using enzyme-linked immunosorbent assay (ELISA) for IgG to spike trimer, which was modified from an assay4 to give a readout of half-maximal binding titers. The reciprocal half-maximal binding titers represent the dilution of plasma that achieves 50% of maximal binding of a known control that reaches saturation. Day 0 and 14 samples from vaccinees were also tested for ID99 (the 99% inhibitory dose, the highest dilution at which 99% of cells were protected) by live virus neutralization (presented as reciprocals).5 Samples from each day were compared between each prior Ab-positive (asymptomatic or symptomatic) group to the Ab-negative group.

    All health care workers provided written informed consent; the study was approved by the University of Maryland institutional review board. Statistical analysis was performed with GraphPad Prism 5 (GraphPad Software). Antibody titers between groups were tested using the 2-tailed Mann-Whitney test, with P < .05 considered significant.

    Results

    Of 3816 health care workers enrolled in the serosurvey study,3 151 were randomly contacted and 59 volunteers enrolled: 17 in the Ab-negative, 16 in the asymptomatic, and 26 in the symptomatic group (Table). The median age was 38 years for the Ab-negative, 40 years for the asymptomatic, and 38 years for the symptomatic group. The percentage of women was 71% for the Ab-negative, 75% for the asymptomatic, and 88% for the symptomatic group. At 0, 7, and 14 days, median reciprocal half-maximal binding titers were higher in each of the asymptomatic (208, 29 364, and 34 033) and symptomatic (302, 32 301, and 35 460) groups compared with the Ab-negative group (<50, <50, and 924) (P < .001 for each). At 0 and 14 days, median reciprocal ID99 virus neutralization titers of each of the asymptomatic (80 and 40 960) and symptomatic (320 and 40 960) groups were higher than the Ab-negative group (<20 and 80) (P < .001 for each) (Figure).

    Discussion

    Health care workers with previous COVID-19 infection, based on laboratory-confirmed serology testing, had higher antibody titer responses to a single dose of mRNA vaccine than those who were not previously infected. Antibody titers started peaking at 7 days and achieved higher titers and neutralization in 14 days compared with Ab-negative volunteers. Limitations of the study are the small sample size, lack of demonstration of vaccine efficacy, and potential bias introduced by those enrolling not being representative of the larger original population. Given the ongoing worldwide vaccine shortages, the results inform suggestions for a single-dose vaccination strategy for those with prior COVID-19 or placing them lower on the vaccination priority list.6

    Section Editor: Jody W. Zylke, MD, Deputy Editor.
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    Article Information

    Accepted for Publication: February 22, 2021.

    Published Online: March 1, 2021. doi:10.1001/jama.2021.3341

    Corresponding Author: Mohammad M. Sajadi, MD, Institute of Human Virology, Global Virus Network Center of Excellence, University of Maryland School of Medicine, 725 W Lombard St (N548), Baltimore, MD 21201 (msajadi@ihv.umaryland.edu).

    Author Contributions: Dr Sajadi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Harris and Sajadi are co–senior authors.

    Concept and design: Newman, Harris, Sajadi.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Frieman, Harris, Sajadi.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Rikhtegaran Tehrani, Frieman, Harris, Sajadi.

    Obtained funding: Frieman, Harris.

    Administrative, technical, or material support: Saadat, Rikhtegaran Tehrani, Newman, Frieman, Sajadi.

    Supervision: Frieman, Sajadi.

    Conflict of Interest Disclosures: Dr Harris reported receiving grants from CDC Covid Supplement during the conduct of the study. No other disclosures were reported.

    Additional Contributions: We thank all of the study participants who donated their time and samples.

    References
    1.
    Winter  L. US officials debate efficacy of half doses of COVID-19 vaccine. The Scientist. Published January 5, 2021. Accessed February 13, 2021. https://www.the-scientist.com/news-opinion/us-officials-debate-efficacy-of-half-doses-of-covid-19-vaccine-68316
    2.
    Dan  JM, Mateus  J, Kato  Y,  et al.  Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.   Science. 2021;371(6529):eabf4063. doi:10.1126/science.abf4063PubMedGoogle Scholar
    3.
    Mullins  KE, Merrill  V, Ward  M,  et al.  Validation of COVID-19 serologic tests and large scale screening of asymptomatic healthcare workers.   Clin Biochem. 2021;S0009-9120(21)00005-9.PubMedGoogle Scholar
    4.
    Rikhtegaran Tehrani  Z, Saadat  S, Saleh  E,  et al.  Performance of nucleocapsid and spike-based SARS-CoV-2 serologic assays.   PLoS One. 2020;15(11):e0237828. doi:10.1371/journal.pone.0237828PubMedGoogle Scholar
    5.
    Keech  C, Albert  G, Cho  I,  et al.  Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine.   N Engl J Med. 2020;383(24):2320-2332. doi:10.1056/NEJMoa2026920PubMedGoogle ScholarCrossref
    6.
    Haute Autorité de Santé (HAS). Stratégie de vaccination contre le SARS-CoV-2: vaccination des personnes ayant un antécédent de Covid-19 [SARS-CoV-2 vaccination strategy: vaccination of people with a history of Covid-19]. Published February 11, 2021. Accessed February 13, 2021. https://www.has-sante.fr/upload/docs/application/pdf/2021-02/strategie_de_vaccination_contre_le_sars-cov-2___vaccination_des_personnes_ayant_un_antecedent_de_covid-19_-_synthese.pdf
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