key: cord-0890780-wzqjaaz9 authors: Wei, J.; Stoesser, N.; Matthews, P. C.; Studley, R.; Bell, I.; Bell, J. I.; Newton, J. N.; Farrar, J.; Diamond, I.; Rourke, E.; Howarth, A.; Marsden, B. D.; Hoosdally, S.; Jones, E. Y.; Stuart, D. I.; Crook, D. W.; Peto, T. E.; Pouwels, K. B.; Eyre, D. W.; Walker, A. S.; team, COVID-19 Infection Survey title: The impact of SARS-CoV-2 vaccines on antibody responses in the general population in the United Kingdom date: 2021-04-23 journal: nan DOI: 10.1101/2021.04.22.21255911 sha: 683abd9e017c3a73c7015d391bb1e7fab74b4173 doc_id: 890780 cord_uid: wzqjaaz9 Real-world data on antibody response post-vaccination in the general population are limited. 45,965 adults in the UK's national COVID-19 Infection Survey receiving Pfizer-BioNTech or Oxford-AstraZeneca vaccines had 111,360 anti-spike IgG measurements. Without prior infection, seroconversion rates and quantitative antibody levels post single dose were lower in older individuals, especially >60y. Two doses achieved high responses across all ages, particularly increasing seroconversion in older people, to similar levels to those achieved after prior infection followed by a single dose. Antibody levels rose more slowly and to lower levels with Oxford-AstraZeneca vs Pfizer-BioNTech, but waned following a single Pfizer-BioNTech dose. Latent class models identified four responder phenotypes: older people, males, and those having long-term health conditions were more commonly 'low responders'. Where supplies are limited, vaccines should be prioritised for those not previously infected, and second doses to individuals >60y. Further data on the relationship between vaccine-mediated protection and antibody responses are needed. , . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) R e s u l t s 4 5 , 9 6 5 p a r t i c i p a n t s a g e d ≥ 1 6 y e a r s f r o m t h e g e n e r a l p o p u l a t i o n w h o w e r e f i r s t v a c c i n a t e d b e t w e e n 8 D e c e m b e r 2 0 2 0 a n d 6 A p r i l 2 0 2 1 c o n t r i b u t e d a t o t a l o f 1 1 1 , 3 6 0 S A R S -C o V -2 a n t i -s p i k e I g G m e a s u r e m e n t s t a k e n a t a n y p o i n t b e t w e e n 9 1 d a y s b e f o r e f i r s t v a c c i n a t i o n d a t e t h r o u g h t o 6 A p r i l 2 0 2 1 . T h e m e d i a n ( I Q R f i z e r -B i o N T e c h , t h e m e d i a n ( I Q R ) d u r a t i o n b e t w e e n t w o d o s e s w a s 3 1 ( 2 1 -4 7 ) d a y s , w i t h 1 , 0 2 0 ( 5 4 . 6 % ) ≤ 3 1 d a y s ( F i g u r e 1 , T a b l e S 1 ) . P a r t i c i p a n t c h a r a c t e r i s t i c s v a r i e d a c r o s s t h e d i f f e r e n t v a c c i n a t i o n g r o u . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. ; https://doi.org/10.1101/2021.04.22.21255911 doi: medRxiv preprint . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. ; https://doi.org/10.1101/2021.04.22.21255911 doi: medRxiv preprint a c c i n e , h i g h a n t i -s p i k e I g G l e v e l s w e r e a c h i e v e d 2 8 d a y s a f t e r t h e L a t e n t c l a s s a n a l y . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. f i n d i n g s a r e c o n s i s t e n t w i t h o b s e r v a t i o n s t h a t f e m a l e s g e n e r a t e s t r o n g e r h u m o r a l i m m u n i t y a n d g r e a t e r v a c c i n e e f f i c a c y t h a n m a l e s o l d e r p a r t i c i p a n t s a n d t h o s e w i t h l o n g t e r m h e a l t h c o n d i t i o n s , b u t c o m p r i s e d a s i m i l a r p e r c e n t a g e r e c e i v i n g t h e d i f f e r e n t v a c c i n e s , s u g g e s t i n g a c o m m o n b i o l o g i c a l c a u s . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. ; https://doi.org/10.1101/2021.04.22.21255911 doi: medRxiv preprint 0 t h e s t u d y . W e u s e d m u l t i v a r i a b l e l o g i s t i c a n d l i n e a r g e n e r a l i z e d a d d i t i v e m o d e l s ( G A M s ) t o i n v e s t i g a t e b i n a r y ( p o s i t i v e / n e g a t i v e ) a n d q u a n t i t a t i v e ( l o g 1 0 ( m A b 4 5 u n i t s ) ) a n t i -s p i k e I g G a n t i b o d y m e a s u r e m e n t . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. ; https://doi.org/10.1101/2021.04.22.21255911 doi: medRxiv preprint 1 T o i n v e s t i g a t e p r e d i c t o r s o f a n t i b o d y r e s p o n s e i n t h o s e w i t h o u t p r i o r e v i d e n c e o f i n f e c t i o n , w e c o n s i d e r e . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. ; https://doi.org/10.1101 https://doi.org/10. /2021 preprint p a r t i c i p a n t w a s a h e a l t h c a r e w o r k e r w e r e i n c l u d e d a s c o v a r i a t e s f o r c l a s s m e m b e r s h i p . T h e n u m b e r o f c l a s s e s w a s d e t e r m i n e d b y m i n i m i z i n g t h e B a y e s i a n i n f o r m a t i o n c r i t e r i o n ( B I C ) f o r e a c h v a c c i . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. C o m p e t i n g I n t e r e s t s s t a t e m e n t D W E d e c l a r e s l e c t u r e f e e s f r o m G i l e a d , o u t s i d e t h e s u b m i t t e d w o r k . N o o t h e r a u t h o r h a s a c o n f l i c t o . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 23, 2021. e d i c i n e s a n d H e a l t h c a r e p r o d u c t s R e g u l a t o r y A g e n c y . R e g u l a t o r y a p p r o v a l o f P f i z e r / B i o N T e c h v a c c i n e f o r C O V I D -1 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 23, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 23, 2021. ; https://doi.org/10.1101/2021.04.22.21255911 doi: medRxiv preprint internal knots placed at 20 th , 40 th , 60 th , and 80 th percentile (30, 44, 57, 71 years) and two boundary knots at 5 th and 95 th percentile (19, 82 years). Test for interaction between sex and age p=0.02. Plotted at reference category for other variables (Pfizer one dose (Panel A)/female (Panel B), white ethnicity, IMD=55, household size=1, did not work in patient-facing healthcare or social care, did not work in a care home, no long-term health condition). . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 23, 2021. ; https://doi.org/10.1101/2021.04.22.21255911 doi: medRxiv preprint Supplementary Table 3 . Class 1='plausibly previously infected' group (3.9% AZ, 3.9% Pfizer), 2='high response' group (31.6% AZ, 63.5% Pfizer), 3='medium response' group (58.7% AZ, 27.5% Pfizer), 4='low response group' (5.8% AZ, 5.1% Pfizer) . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 23, 2021. ; https://doi.org/10.1101/2021.04.22.21255911 doi: medRxiv preprint Table 1 . Predictors of antibody positivity 14-60 days post first vaccination in participants without evidence of prior infection from univariable and multivariable logistic regression models. AZ: Oxford-AstraZeneca vaccine. Pfizer: Pfizer-BioNTech vaccine. Line colour indicates antibody response predicted for ages 20, 40, 60, and 80 years (see Figure S1 for full model across all ages and Figure S2 for comparisons of vaccine type by age). The bars in 'Two doses Pfizer-BioNTech' plot show the percentage of people having had two doses of vaccines by each timepoint (Gray: had two doses; Blue: had only one dose) Line colour indicates response predicted for ages 20, 40, 60, and 80 years (see Figure S8 for all ages and Figure 4 for comparisons of vaccine type by age). The bars in 'Two doses Pfizer-BioNTech' plot show the percentage of people having had two doses of vaccines by each timepoint