Наблюдения от японцев
Jan. 30th, 2022 11:46 pm![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
chuka_lisАвторы исследования проверили состояние иммунитета (титры антител у 608 человек, и реакция Т-клеточного иммунитета на стимуляцию вирусом, QuantiFERON, у 536 из них же) среди японских медработников, получивших 2 дозы мРНК вакцины. Так же они проверили группу на антитела к капсидному белку, дабы выявить вероятные инфекции(пробои) у тех, кто отмечал в прошлом симптомы ОРЗ да и вообще.
Выяснилось, что пик иммунного ответа наблюдался в период через 3 недели после 2 прививки, и к 6 месяцам, иммунный ответ, что антительный, что Тклеточный, снизился очень серьезно: раз в 10-15 для антител и около 2 раз для Т-клеток. Снижение 2 фракций иммунитета было синхронным.
Обнаружили 6 пробоев, 1 из которых был симптоматичный, 1- контактник, у которого был отрицательный ПЦР при тестировании. Из тех, что известны с симптомами или контактом- то "пробой" случился через 4-5 мес после прививки. Те четверо, что "асимптоматичные", видимо, все же не совсем уж асимптоматичные, потому что, судя по историям, их пробои случились около 3 мес после прививки. Вообще же, у тех, кто заболел (как видим- легко и асимптоматично) титры антител и реакции Т-клеток были после прививки примерно такие же как и у других.
Все с пробоями были женщины, без хронических заболеваний и с нормальным иммунитетом.
Так что за 6 месяцев пробой случился у каждого сотого привитого.
В приницпе, это немного; с другой стороны- это всего в период полгода после прививки и когда еще не было омикрона. Авторы думают, что причина пробоев- не то, что иммунитет ослабел, а то, что увеличилась "контактность" с носителями или больными, по работе итп, тк тогда пошла волна случаев, связанных с олимпиадой и туристами.
Характерно, что титры антител у тех, у кого был пробой, как и их нейтрализующая активность, через 6 месяцев были выше, чем у тех, кто без пробоев, и выше, чем было в среднем через 3 недели после полной прививки- так что асимптоматическая инфекция послужила "бустером" для гуморального иммунитета. Только для него- тк в состоянии клеточного отличий не обнаружилось.
The waning of the antibody titre after the first two doses of the Pfizer-BioNTech BNT162b2 mRNA SARS-CoV-2 vaccine was reported. However, knowledge of the dynamics of cellular immunity is scarce. Here, we performed a prospective cohort study to disclose antibody and cellular immunity dynamics and discuss the relationship between immunity and breakthrough infection. Methods The study had a prospective cohort design. Antibody titres against SARS-CoV-2 in serially collected serum samples of 608 Japanese vaccinees after 6 months of vaccination were measured. Simultaneously, T-cell immunity dynamics were assessed using the QuantiFERON SARS-CoV-2 assay. Additionally, participants with suspected breakthrough infection were detected according to the positive conversion of the IgG assay for nucleocapsid proteins of SARS-CoV-2. Results Antibody titres were elevated 3 weeks after vaccination and waned over the remainder of the study period. The QuantiFERON SARS-CoV-2 assay performed on 536 participants demonstrated the similar dynamics. Six participants without predisposing medical conditions demonstrated positive conversion of the IgG assay for nucleocapsid proteins, while five were asymptomatic. The antibody titres before vaccination were 9.8 ± 109.1 AU/mL in Alinity RBD-IgG, 0.2 ± 3.6 SU/mL in HISCL S-IgG and 1.0 ± 0.6 U/mL in STACIA Neut-Ab. After 3 weeks of vaccination the antibody titres increased to 15,443.5 ± 9,655.2 AU/mL in Alinity RBD-IgG, 406.0 ± 242.7 SU/mL in HISCL S-IgG, and 23.6 ± 14.1 U/mL in STACIA Neut-Ab. Antibody titres waned with time after vaccination and that after 6 months from vaccination were 1,576.8 ± 5080.2 AU/mL in Alinity RBDIgG, 63.9 ± 195.9 SU/mL in HISCL S-IgG, and 3.3 ± 4.9 U/mL in STACIA Neut-Ab (Fig 1). Correlation analysis among the Alinity RBD-IgG, HISCL S-IgG, and STACIA Neut-Ab test results of all samples collected in the study demonstrated sufficiently high correlations. The QuantiFERON SARS-CoV-2 assay results demonstrated similar dynamics. Before vaccination, the assay was performed for 536 participants and IFN for Ag1 was 0.00 ± 0.08 IU/mL and IFN for Ag2 was 0.01 ± 0.07 IU/mL. After 8 weeks, IFN for Ag1 and IFN for Ag2 increased to 0.66 ± 0.87 IU/mL and 1.06 ± 1.25 IU/mL, respectively. However, IFN for Ag1 and IFN for Ag2 decreased to 0.37 ± 0.63 IU/mL and 0.62 ± 0.99 IU/mL, respectively, within 6 months after vaccination (Fig 2). The mean N-IgG titre was 0.6 ± 9.5 SU/mL before vaccination. The titre was not affected by the vaccination: 0.7 ± 8.4 SU/mL, 0.4 ± 4.7 SU/mL, and 0.3 ± 3.5 SU/mL after 3 weeks, 8 weeks, and 3 months of vaccination, respectively (Supplement Fig S2). After 6 months of vaccination, mean titre was 0.9 ± 8.9 SU/mL; however, six participants turned positive serologically and had suspected breakthrough infection.All six participants with suspected breakthrough infection were female, without pre-existing illnesses or immunosuppressant use. One participant was diagnosed with COVID-19 according to the PCR test results performed 4 months after vaccination. One participant had close contact with COVID-19 patients after 5 months from vaccination; however, the PCR test result was negative. The other four participants were asymptomatic and had no history of close contact with patients with COVID-19 (Table 2). Compared with participants without suspected breakthrough, antibody titres before the breakthrough (after 3 month of vaccination) were equivalent, but titres after the breakthrough (after 6 month of vaccination) were significantly higher. However, the QuantiFERON results were not affected even after breakthrough The measurement of N-IgG made it possible to detect five asymptomatic breakthrough infections in the present study. One of them was subjected to PCR testing, but the result was negative. Although the negativity may be attributed to the sensitivity of PCR tests, it is plausible that a faster mean rate of viral load decline in fully vaccinated individuals than in unvaccinated individuals might give rise to a negative result [12]. The median antibody titre of participants with suspected breakthrough 3 months after vaccination was not lower than that of those without breakthrough infections. This suggests that breakthrough infections may occur not only in poor responders but also in good responders several months after BNT162b2 vaccination. Otherwise, the median antibody titre using STACIA Neut-Ab after 6 months of vaccination (51.2 U/mL) being higher than that after 3 weeks of vaccination (31.9 U/mL) seems to provide evidence that asymptomatic breakthrough infections exert a sufficient booster effect, consistent with observations previously obtained from breakthrough infections confirmed by PCR tests. Notably, the IGRA results were not affected by breakthrough infections in the present study. This is similar to a report by Kato et al. [4] on discrepant antibody titres and IGRA results due to breakthrough infection. As the reason for the discrepancy between the antibody titres and the IGRA results has not been determined, further studies are warranted. Conclusion Waning of humoral and cellular immunity within 6 months of administration of two doses of BNT162b2 vaccine among Japanese healthcare professionals and the occurrence of asymptomatic breakthrough infection was suspected in approximately 1 of 100 vaccinees.
Выяснилось, что пик иммунного ответа наблюдался в период через 3 недели после 2 прививки, и к 6 месяцам, иммунный ответ, что антительный, что Тклеточный, снизился очень серьезно: раз в 10-15 для антител и около 2 раз для Т-клеток. Снижение 2 фракций иммунитета было синхронным.
Обнаружили 6 пробоев, 1 из которых был симптоматичный, 1- контактник, у которого был отрицательный ПЦР при тестировании. Из тех, что известны с симптомами или контактом- то "пробой" случился через 4-5 мес после прививки. Те четверо, что "асимптоматичные", видимо, все же не совсем уж асимптоматичные, потому что, судя по историям, их пробои случились около 3 мес после прививки. Вообще же, у тех, кто заболел (как видим- легко и асимптоматично) титры антител и реакции Т-клеток были после прививки примерно такие же как и у других.
Все с пробоями были женщины, без хронических заболеваний и с нормальным иммунитетом.
Так что за 6 месяцев пробой случился у каждого сотого привитого.
В приницпе, это немного; с другой стороны- это всего в период полгода после прививки и когда еще не было омикрона. Авторы думают, что причина пробоев- не то, что иммунитет ослабел, а то, что увеличилась "контактность" с носителями или больными, по работе итп, тк тогда пошла волна случаев, связанных с олимпиадой и туристами.
Характерно, что титры антител у тех, у кого был пробой, как и их нейтрализующая активность, через 6 месяцев были выше, чем у тех, кто без пробоев, и выше, чем было в среднем через 3 недели после полной прививки- так что асимптоматическая инфекция послужила "бустером" для гуморального иммунитета. Только для него- тк в состоянии клеточного отличий не обнаружилось.
The waning of the antibody titre after the first two doses of the Pfizer-BioNTech BNT162b2 mRNA SARS-CoV-2 vaccine was reported. However, knowledge of the dynamics of cellular immunity is scarce. Here, we performed a prospective cohort study to disclose antibody and cellular immunity dynamics and discuss the relationship between immunity and breakthrough infection. Methods The study had a prospective cohort design. Antibody titres against SARS-CoV-2 in serially collected serum samples of 608 Japanese vaccinees after 6 months of vaccination were measured. Simultaneously, T-cell immunity dynamics were assessed using the QuantiFERON SARS-CoV-2 assay. Additionally, participants with suspected breakthrough infection were detected according to the positive conversion of the IgG assay for nucleocapsid proteins of SARS-CoV-2. Results Antibody titres were elevated 3 weeks after vaccination and waned over the remainder of the study period. The QuantiFERON SARS-CoV-2 assay performed on 536 participants demonstrated the similar dynamics. Six participants without predisposing medical conditions demonstrated positive conversion of the IgG assay for nucleocapsid proteins, while five were asymptomatic. The antibody titres before vaccination were 9.8 ± 109.1 AU/mL in Alinity RBD-IgG, 0.2 ± 3.6 SU/mL in HISCL S-IgG and 1.0 ± 0.6 U/mL in STACIA Neut-Ab. After 3 weeks of vaccination the antibody titres increased to 15,443.5 ± 9,655.2 AU/mL in Alinity RBD-IgG, 406.0 ± 242.7 SU/mL in HISCL S-IgG, and 23.6 ± 14.1 U/mL in STACIA Neut-Ab. Antibody titres waned with time after vaccination and that after 6 months from vaccination were 1,576.8 ± 5080.2 AU/mL in Alinity RBDIgG, 63.9 ± 195.9 SU/mL in HISCL S-IgG, and 3.3 ± 4.9 U/mL in STACIA Neut-Ab (Fig 1). Correlation analysis among the Alinity RBD-IgG, HISCL S-IgG, and STACIA Neut-Ab test results of all samples collected in the study demonstrated sufficiently high correlations. The QuantiFERON SARS-CoV-2 assay results demonstrated similar dynamics. Before vaccination, the assay was performed for 536 participants and IFN for Ag1 was 0.00 ± 0.08 IU/mL and IFN for Ag2 was 0.01 ± 0.07 IU/mL. After 8 weeks, IFN for Ag1 and IFN for Ag2 increased to 0.66 ± 0.87 IU/mL and 1.06 ± 1.25 IU/mL, respectively. However, IFN for Ag1 and IFN for Ag2 decreased to 0.37 ± 0.63 IU/mL and 0.62 ± 0.99 IU/mL, respectively, within 6 months after vaccination (Fig 2). The mean N-IgG titre was 0.6 ± 9.5 SU/mL before vaccination. The titre was not affected by the vaccination: 0.7 ± 8.4 SU/mL, 0.4 ± 4.7 SU/mL, and 0.3 ± 3.5 SU/mL after 3 weeks, 8 weeks, and 3 months of vaccination, respectively (Supplement Fig S2). After 6 months of vaccination, mean titre was 0.9 ± 8.9 SU/mL; however, six participants turned positive serologically and had suspected breakthrough infection.All six participants with suspected breakthrough infection were female, without pre-existing illnesses or immunosuppressant use. One participant was diagnosed with COVID-19 according to the PCR test results performed 4 months after vaccination. One participant had close contact with COVID-19 patients after 5 months from vaccination; however, the PCR test result was negative. The other four participants were asymptomatic and had no history of close contact with patients with COVID-19 (Table 2). Compared with participants without suspected breakthrough, antibody titres before the breakthrough (after 3 month of vaccination) were equivalent, but titres after the breakthrough (after 6 month of vaccination) were significantly higher. However, the QuantiFERON results were not affected even after breakthrough The measurement of N-IgG made it possible to detect five asymptomatic breakthrough infections in the present study. One of them was subjected to PCR testing, but the result was negative. Although the negativity may be attributed to the sensitivity of PCR tests, it is plausible that a faster mean rate of viral load decline in fully vaccinated individuals than in unvaccinated individuals might give rise to a negative result [12]. The median antibody titre of participants with suspected breakthrough 3 months after vaccination was not lower than that of those without breakthrough infections. This suggests that breakthrough infections may occur not only in poor responders but also in good responders several months after BNT162b2 vaccination. Otherwise, the median antibody titre using STACIA Neut-Ab after 6 months of vaccination (51.2 U/mL) being higher than that after 3 weeks of vaccination (31.9 U/mL) seems to provide evidence that asymptomatic breakthrough infections exert a sufficient booster effect, consistent with observations previously obtained from breakthrough infections confirmed by PCR tests. Notably, the IGRA results were not affected by breakthrough infections in the present study. This is similar to a report by Kato et al. [4] on discrepant antibody titres and IGRA results due to breakthrough infection. As the reason for the discrepancy between the antibody titres and the IGRA results has not been determined, further studies are warranted. Conclusion Waning of humoral and cellular immunity within 6 months of administration of two doses of BNT162b2 vaccine among Japanese healthcare professionals and the occurrence of asymptomatic breakthrough infection was suspected in approximately 1 of 100 vaccinees.
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