학술논문
Serum Neutralizing Antibody Titers 12 Months After Coronavirus Disease 2019 Messenger RNA Vaccination: Correlation to Clinical Variables in an Adult, US Population.
Document Type
Academic Journal
Author
Zhao M; Department of Medicine, Division of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut, USA.; Slotkin R; Yale School of Public Health, New Haven, Connecticut, USA.; Sheth AH; Yale School of Medicine, New Haven, Connecticut, USA.; Pischel L; Department of Medicine, Division of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut, USA.; Yale School of Public Health, New Haven, Connecticut, USA.; Kyriakides TC; Department of Veterans Affairs Office of Research and Development, Cooperative Studies Program Coordinating Center, West Haven, Connecticut, USA.; Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, Connecticut, USA.; Emu B; Department of Medicine, Division of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut, USA.; Department of Medicine, Division of Infectious Diseases, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; McNamara C; Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.; Shi Q; Department of Medicine, Division of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut, USA.; Delgobbo J; Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; University of Connecticut, Storrs, Connecticut, USA.; Xu J; Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.; Marhoffer E; Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.; Mercer-Falkoff A; Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.; Holleck J; Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.; Ardito D; Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; Sutton RE; Department of Medicine, Division of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut, USA.; Department of Medicine, Division of Infectious Diseases, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; Gupta S; Department of Medicine, Division of Infectious Diseases, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; Department of Medicine, Veterans Affairs Healthcare Systems of Connecticut, West Haven, Connecticut, USA.; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 9203213 Publication Model: Print Cited Medium: Internet ISSN: 1537-6591 (Electronic) Linking ISSN: 10584838 NLM ISO Abbreviation: Clin Infect Dis Subsets: MEDLINE
Subject
Language
English
Abstract
Background: We studied whether comorbid conditions affect strength and duration of immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA vaccination in a US-based, adult population.
Methods: Sera (before and after BNT162b2 vaccination) were tested serially up to 12 months after 2 doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Postbooster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects, respectively.
Results: After completion of primary vaccine series, neutralizing antibody half maximal inhibitory concentration (IC50) values were high at 1 month (14-fold increase from prevaccination), declined at 6 months (3.3-fold increase), and increased at 1 month postbooster (41.5-fold increase). Three months postbooster, IC50 decreased in coronavirus disease (COVID)-naïve individuals (18-fold increase) and increased in prior COVID 2019 (COVID-19+) individuals (132-fold increase). Age >65 years (β = -0.94, P = .001) and malignancy (β = -0.88, P = .002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively affected by end-stage renal disease ([β = -1.10, P = .004]; [β = -0.66, P = .014]), diabetes mellitus ([β = -0.57, P = .032]; [β = -0.44, P = .028]), and systemic steroid use ([β = -0.066, P = .032]; [β = -0.55, P = .037]). Postbooster IC50 was robust against WA-1 and B.1.617.2. Postbooster neutralization increased with prior COVID-19 (β = 2.9, P < .0001), and malignancy reduced neutralization response (β = -0.68, P = .03), regardless of infection status.
Conclusions: Multiple clinical factors affect the strength and duration of neutralization response after primary series vaccination, but not the postbooster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens.
Competing Interests: Potential conflicts of interest. None of the authors declare any conflict of interests: Q. S. reports support for the present manuscript from VA Connecticut Research and Education Foundation. E. M. and S. G. report being members of IRB committee at West Haven VA, recused themselves during discussion of study. R. S. reports support for the present manuscript from WHVA Research Service and serving on DSMB for Moderna for several clinical mRNA vaccine studies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2022.)
Methods: Sera (before and after BNT162b2 vaccination) were tested serially up to 12 months after 2 doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Postbooster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects, respectively.
Results: After completion of primary vaccine series, neutralizing antibody half maximal inhibitory concentration (IC50) values were high at 1 month (14-fold increase from prevaccination), declined at 6 months (3.3-fold increase), and increased at 1 month postbooster (41.5-fold increase). Three months postbooster, IC50 decreased in coronavirus disease (COVID)-naïve individuals (18-fold increase) and increased in prior COVID 2019 (COVID-19+) individuals (132-fold increase). Age >65 years (β = -0.94, P = .001) and malignancy (β = -0.88, P = .002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively affected by end-stage renal disease ([β = -1.10, P = .004]; [β = -0.66, P = .014]), diabetes mellitus ([β = -0.57, P = .032]; [β = -0.44, P = .028]), and systemic steroid use ([β = -0.066, P = .032]; [β = -0.55, P = .037]). Postbooster IC50 was robust against WA-1 and B.1.617.2. Postbooster neutralization increased with prior COVID-19 (β = 2.9, P < .0001), and malignancy reduced neutralization response (β = -0.68, P = .03), regardless of infection status.
Conclusions: Multiple clinical factors affect the strength and duration of neutralization response after primary series vaccination, but not the postbooster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens.
Competing Interests: Potential conflicts of interest. None of the authors declare any conflict of interests: Q. S. reports support for the present manuscript from VA Connecticut Research and Education Foundation. E. M. and S. G. report being members of IRB committee at West Haven VA, recused themselves during discussion of study. R. S. reports support for the present manuscript from WHVA Research Service and serving on DSMB for Moderna for several clinical mRNA vaccine studies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2022.)