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1.
J Infect Chemother ; 28(9): 1273-1278, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1966847

ABSTRACT

INTRODUCTION: The vaccine against SARS-CoV-2 provides humoral immunity to fight COVID-19; however, the acquired immunity gradually declines. Booster vaccination restores reduced humoral immunity; however, its effect on newly emerging variants, such as the Omicron variant, is a concern. As the waves of COVID-19 cases and vaccine programs differ between countries, it is necessary to know the domestic effect of the booster. METHODS: Serum samples were obtained from healthcare workers (20-69 years old) in the Pfizer BNT162b2 vaccine program at the Toyama University Hospital 6 months after the second dose (6mA2D, n = 648) and 2 weeks after the third dose (2wA3D, n = 565). The anti-SARS-CoV-2 antibody level was measured, and neutralization against the wild-type and variants (Delta and Omicron) was evaluated using pseudotyped viruses. Data on booster-related events were collected using questionnaires. RESULTS: The median anti-SARS-CoV-2 antibody was >30.9-fold elevated after the booster (6mA2D, 710.0 U/mL [interquartile range (IQR): 443.0-1068.0 U/mL]; 2wA3D, 21927 U/mL [IQR: 15321.0->25000.0 U/mL]). Median neutralizing activity using 100-fold sera against wild-type-, Delta-, and Omicron-derived variants was elevated from 84.6%, 36.2%, and 31.2% at 6mA2D to >99.9%, 99.1%, and 94.6% at 2wA3D, respectively. The anti-SARS-CoV-2 antibody levels were significantly elevated in individuals with fever ≥37.5 °C, general fatigue, and myalgia, local swelling, and local hardness. CONCLUSION: The booster effect, especially against the Omicron variant, was observed in the Japanese population. These findings contribute to the precise understanding of the efficacy and side effects of the booster and the promotion of vaccine campaigns.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19 , Adult , Aged , BNT162 Vaccine/immunology , COVID-19/prevention & control , Humans , Japan , Middle Aged , SARS-CoV-2 , Vaccines, Inactivated , Young Adult
2.
Viruses ; 14(7)2022 06 27.
Article in English | MEDLINE | ID: covidwho-1911656

ABSTRACT

The effects of casirivimab and imdevimab (C/I) on the innate immune response against SARS-CoV-2 infection remain unclear. We evaluated the effect of C/I on type I interferon (IFN-I) and cytokines in patients with SARS-CoV-2 infection. This prospective observational study recruited consecutive patients hospitalized with SARS-CoV-2 infection. Blood levels of IFN-I and cytokines before and after C/I administration were assessed using enzyme-linked immunoassay. The study enrolled 29 patients in the C/I group. In addition, 11 patients who received remdesivir and dexamethasone (R/D group) during the early phase (≤5 days after the onset of symptoms) were included as a comparator group. After treatment, IFN-α and IFN-ß levels decreased significantly in both the C/I group and R/D group, whilst the post-treatment neutrophil-to-lymphoid ratio increased in the early C/I group but not the R/D group. In the C/I group, temporal temperature elevation and hypoxemia were observed after treatment in 58.6% and 41.4% of the cohort, respectively. However, most patients recovered by 5 days after treatment. This study could demonstrate the high therapeutic effect of C/I with an antibody-dependent enhancement-like response and decreased IFN-I production, which was likely due to the immediate induction of an antibody-dependent immune response against SARS-CoV-2.


Subject(s)
COVID-19 , Interferon Type I , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , Cytokines , Humans , Interferon Type I/pharmacology , Interferon Type I/therapeutic use , SARS-CoV-2
3.
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy ; 2022.
Article in English | EuropePMC | ID: covidwho-1887898

ABSTRACT

Introduction The vaccine against SARS-CoV-2 provides humoral immunity to fight COVID-19;however, the acquired immunity gradually declines. Booster vaccination restores reduced humoral immunity;however, its effect on newly emerging variants, such as the Omicron variant, is a concern. As the waves of COVID-19 cases and vaccine programs differ between countries, it is necessary to know the domestic effect of the booster. Methods Serum samples were obtained from healthcare workers (20–69 years old) in the Pfizer BNT162b2 vaccine program at the Toyama University Hospital 6 months after the second dose (6mA2D, n = 648) and 2 weeks after the third dose (2wA3D, n = 565). The anti-SARS-CoV-2 antibody level was measured, and neutralization against the wild-type and variants (Delta and Omicron) was evaluated using pseudotyped viruses. Data on booster-related events were collected using questionnaires. Results The median anti-SARS-CoV-2 antibody was >30.9-fold elevated after the booster (6mA2D, 710.0 U/mL [interquartile range (IQR): 443.0–1068.0 U/mL];2wA3D, 21927 U/mL [IQR: 15321.0–>25000.0 U/mL]). Median neutralizing activity using 100-fold sera against wild-type-, Delta-, and Omicron-derived variants was elevated from 84.6%, 36.2%, and 31.2% at 6mA2D to >99.9%, 99.1%, and 94.6% at 2wA3D, respectively. The anti-SARS-CoV-2 antibody levels were significantly elevated in individuals with fever ≥37.5 °C, general fatigue, and myalgia, local swelling, and local hardness. Conclusion The booster effect, especially against the Omicron variant, was observed in the Japanese population. These findings contribute to the precise understanding of the efficacy and side effects of the booster and the promotion of vaccine campaigns.

5.
MAbs ; 14(1): 2072455, 2022.
Article in English | MEDLINE | ID: covidwho-1839974

ABSTRACT

Many potent neutralizing SARS-CoV-2 antibodies have been developed and used for therapies. However, the effectiveness of many antibodies has been reduced against recently emerging SARS-CoV-2 variants, especially the Omicron variant. We identified a highly potent SARS-CoV-2 neutralizing antibody, UT28K, in COVID-19 convalescent individuals who recovered from a severe condition. UT28K showed efficacy in neutralizing SARS-CoV-2 in an in vitro assay and in vivo prophylactic treatment, and the reactivity to the Omicron strain was reduced. The structural analyses revealed that antibody UT28K Fab and SARS-CoV-2 RBD protein interactions were mainly chain-dominated antigen-antibody interactions. In addition, a mutation analysis suggested that the emergence of a UT28K neutralization-resistant SARS-CoV-2 variant was unlikely, as this variant would likely lose its competitive advantage over circulating SARS-CoV-2. Our data suggest that UT28K offers potent protection against SARS-CoV-2, including newly emerging variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Humans
6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329205

ABSTRACT

Introduction The vaccine against SARS-CoV-2 provides humoral immunity to fight COVID-19;however, the acquired immunity gradually declines. Booster vaccination restores reduced humoral immunity;however, its effect on newly emerging variants, such as the Omicron variant, is a concern. As the waves of COVID-19 cases and vaccine programs differ between countries, it is necessary to know the domestic effect of the booster. Methods Serum samples were obtained from healthcare workers (20-69 years old) in the Pfizer BNT162b2 vaccine program at the Toyama University Hospital 6 months after the second dose (6mA2D, n = 648) and 2 weeks after the third dose (2wA3D, n = 565). The anti-SARS-CoV-2 antibody level was measured, and neutralization against the wild-type and variants (Delta and Omicron) was evaluated using pseudotyped viruses. Data on booster-related events were collected using questionnaires. Results The median anti-SARS-CoV-2 antibody was >30.9-fold elevated after the booster (6mA2D, 710.0 U/mL [interquartile range (IQR): 443.0–1068.0 U/mL];2wA3D, 21927 U/mL [IQR: 15321.0–>25000.0 U/mL]). Median neutralizing activity using 100-fold sera against wild-type-, Delta-, and Omicron-derived variants was elevated from 84.6%, 36.2%, and 31.2% at 6mA2D to >99.9%, 99.1%, and 94.6% at 2wA3D, respectively. The anti-SARS-CoV-2 antibody levels were significantly elevated in individuals with fever ≥37.5 °C, general fatigue, and myalgia, local swelling, and local hardness. Conclusion The booster effect, especially against the Omicron variant, was observed in the Japanese population. These findings contribute to the precise understanding of the efficacy and side effects of the booster and the promotion of vaccine campaigns.

7.
Microbiol Spectr ; 9(3): e0056121, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1546468

ABSTRACT

Vaccines against severe acute respiratory syndrome coronavirus-2 have been introduced. To investigate the relationship between vaccine-induced humoral immunity and patient age, we measured antibody levels and neutralization in vaccinated sera. Sera from 13 to 17 days after the second dose of the BNT162b2 vaccine were collected from health care workers at the University of Toyama (n = 740). Antibody levels were measured by the anti-receptor binding domain antibody test (anti-RBD test), and neutralization against wild-type (WT), α- and ß-variant pseudotyped viruses were assayed using a high-throughput chemiluminescent reduction neutralizing test (htCRNT; positivity cutoff, 50% neutralization at serum dilution 1:100). Basic clinical characteristics were obtained from questionnaires. Antibodies were confirmed in all participants in both the anti-RBD test (median, 2,112 U/ml; interquartile range [IQR], 1,275 to 3,390 U/ml) and the htCRNT against WT (median % inhibition, >99.9; IQR, >99.9 to >99.9). For randomly selected sera (n = 61), 100.0% had positive htCRNT values against the α- and ß-derived variants. Among those who answered the questionnaire (n = 237), the values of the anti-RBD test were negatively correlated with age in females (P < 0.01). An age-dependent decline in neutralization was observed against the variants but not against the wild-type virus (wild type, P = 0.09; α, P < 0.01; ß, P < 0.01). The neutralizing activity induced by BNT162b2 was obtained not only against the wild-type virus, but also against the variants; however, there was an age-dependent decrease in the latter. Age-related heterogeneity of vaccine-acquired immunity is a concern in preventive strategies in the era dominated by variants. IMPORTANCE Since mRNA vaccines utilize wild-type SARS-CoV-2 spike protein as an antigen, there are potential concerns about acquiring immunity to variants of this virus. The neutralizing activity in BNT162b2-vaccinated individuals was higher against the wild-type virus than against its variants; this effect was more apparent in older age groups. This finding suggests that one of the weaknesses of the mRNA vaccine is the high risk of variant infection in the elderly population. Because the elderly are at a higher risk of SARS-CoV-2 infection, the age-dependent decline of neutralization against viral variants should be considered while planning vaccination programs that include boosters.


Subject(s)
/immunology , COVID-19/immunology , Immunity , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , COVID-19/prevention & control , Cross Reactions , Female , Humans , Immunity, Humoral , Male , Middle Aged , Neutralization Tests , SARS-CoV-2/classification , Spike Glycoprotein, Coronavirus , Vaccination , Young Adult , /immunology
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