key: cord-0280442-6mqxuxuo authors: Alvarez-Diaz, D. A.; Munoz, A. L.; Tavera-Rodriguez, P.; Herrera-Sepulveda, M. T.; Ruiz-Moreno, H. A.; Laiton-Donato, K.; Franco-Munoz, C.; Pelaez-Carvajal, D.; Cuellar, D.; Munoz-Ramirez, A. M.; Galindo, M.; Arias-Ramirez, E. J.; Reyes, M. M. title: Low neutralizing antibody titers against the Mu variant of SARS-CoV-2 in BNT162b2 vaccinated individuals date: 2021-11-19 journal: nan DOI: 10.1101/2021.11.19.21266552 sha: 5589c2451013467d9d63388cd18321f76ed85722 doc_id: 280442 cord_uid: 6mqxuxuo Background Global surveillance programs for the virus that causes COVID-19 are showing the emergence of variants with mutations in the Spike protein, including the Mu variant, recently declared as a Variant of Interest (VOI) by the World Health Organization. Because these types of variants can be more infectious or less susceptible to antiviral treatments and vaccine-induced antibodies. Objectives To evaluate the sensitivity of the Mu variant (B.1.621) to neutralizing antibodies induced by the BNT162b2 vaccine. Study design Three of the most predominant SARS-CoV-2 variants in Colombia during the epidemiological peaks of 2021 were isolated. Microneutralization assays were performed by incubating 120 TCDI50 of each SARS-CoV-2 isolate with five 2-fold serial dilutions of sera from 14 BNT162b2 vaccinated volunteers. The MN50 titer was calculated by the Reed-Muench formula Results The three isolated variants were Mu, a Variant of Interest (VOI), Gamma, a variant of concern (VOC), and B.1.111 that lacks genetic markers associated with greater virulence. At the end of August, the Mu and Gamma variants were widely distributed in Colombia. Mu was predominant (49%), followed by Gamma (25%). In contrast, B.1.111 became almost undetectable. The evaluation of neutralizing antibodies suggests that patients vaccinated with BNT162-2 generate neutralizing antibody titers against the Mu variant at significantly lower concentrations relative to B.1.111 and Gamma. Conclusions This study shows the importance of continuing with surveillance programs of emerging variants as well as the need to evaluate the neutralizing antibody response induced by other vaccines circulating in the country against Mu and other variants with high epidemiological impact. L o w n e u t r a l i z i n g a n t i b o d y t i t e r s a g a i n s t t h e M u v a r i a n t o f S A R S -C o V -2 i n B N T 1 6 2 b 2 v a c c i n a t e d i n d i v i d u a l s D i e g o A . Á l v a r e z -D í a z 1 * , A n a L u i s a M u ñ o z 2 * , P i l a r T a v e r a -R o d r í g u e z 3 * , M a r í a T . H e r r e r a -S e p ú l v e d a 1 , 4 , H e c t o r A l e j a n d r o R u i z -M o r e n o 1 , K a t h e r i n e L a i t o n -D o n a t o 1 , C a r l o s F r a n c o -M u ñ o M u a n d G a m m a v a r i a n t s r e p r e s e n t e d 4 9 % a n d 2 5 % o f c a s e s i n C o l o m b i a b y A u g u s t 2 0 2 1 . • I n c r e a s e d p r o p o r t i o n o f S A R S -C O V -2 c a s e s w e r e m o s t l y a s s o c i a t e d w i t h M u v a r i a n t , d e s p i t e b e i n g d e t e c t e d s i m u l t a n e o u s l y w i t h t h e V O C G a m m a • T h e M u v a r i a n t r e m a r k a b l y e s c a p e s f r o m n e u t r a l i z i n g a n t i b o d i e s e l i c i t e d b y t h e B N T 1 6 2 b 2 v a c c i n e • L a b o r a t o r y s t u d i e s o f n e u t r a l i z i n g a n t i b o d i e s a r e u s e f u l t o d e t e r m i n e t h e e f f i c a c y o f S A R S - C o V - 2 v a c c i n e s a g a i n s t V O C a n d V O I . . CC-BY-NC-ND 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) preprint B a c k g r o u n d G l o b a l s u r v e i l l a n c e p r o g r a m s f o r t h e v i r u s t h a t c a u s e s C O V I D -1 9 a r e s h o w i n g t h e e m e r g e n c e o f v a r i a n t s w i t h m u t a t i o n s i n t h e S p i k e p r o t e i n , i n c l u d i n g t h e M u v a r i a n t , r e c e n t l y d e c l a r e d a V a r i a n t o f I n t e r e s t ( V O I ) b y t h e W o r l d H e a l t h O r g a n i z a t i o n . G e n o m i c a n d l a b o r a t o r y s u r v e i l l a n c e i s i m p o r t a n t i n t h e s e t y p e s o f v a r i a n t s b e c a u s e t h e y m a y b e m o r e i n f e c t i o u s o r l e s s s u s c e p t i b l e t o a n t i v i r a l t r e a t m e n t s a n d v a c c i n e -i n d u c e d a n t i d e m i o l o g i c a l p e a k s o f 2 0 2 1 w e r e i s o l a t e d . M i c r o n e u t r a l i z a t i o n a s s a y s w e r e p e r f o r m e d b y i n c u b a t i n g 1 2 . . CC-BY-NC-ND 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) preprint P r e l i m i n a r y s t u d i e s a s s e s s i n g t h e s e n s i t i v i t y o f t h e M u v a r i a n t t o a n t i b o d i e s i n d u c e d b y t h e B N T 1 6 2 b 2 v a c c i n a t i o n u s i n g p s e u d o v i r u s e s a n d r e p l i c a t i o n -c o m p e t e n t S A R S -C o V -2 y i e l d e d c o n t r a d i c t o r y r e s u l t s [ 6 , 7 ] . I n t h i s s t u d y , w e d e t e r m i n e d t h e n e u t r a l i z a l l o w e d u s t o d e t e r m i n e t h e s p a t i o t e m p o r a l d i s t r i b u t i o n o f t h e m o s t r e p r e s e n t a t i v e S A R S -C o V -2 l i n e a g e s i n C o l o m b i a d u r i n g t h e t w o e p i d e m i o l o g i c a l p e a k s o f S A R S -C o V -2 i n 2 0 2 1 . T h e s e q u e n c e s o b t a i n e d b y p r o b a b i l i s t i c s a m p l i n g i n d i c a t e d a s i g n i f i c a n t i n c r e a s e o . CC-BY-NC-ND 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) preprint p a n e l o f h u m a n s e r a f r o m 1 4 v o l u n t e e r s v a c c i n a t e d w i t h B N T 1 6 2 b 2 ( a g e r a n g e , 2 7 -5 8 y e a r s ) w a s e v a l u a t e d . A n t i -S p i k e I g G a n t i b o d y t i t e r s b u t n o a n t i -n u c l e o p r o t e i n I g G a n t i b o d i e s w e r e i d e n t i f i e d i n a l l s a m p l e s , s u g g e s t i n g t h e e x c l u s i v e p r e s e n c e o f v a c c i n a t i o n -i n d u c e d a n t i b o d i e . CC-BY-NC-ND 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) preprint The copyright holder for this this version posted November 19, 2021. ; https://doi.org/10.1101/2021.11.19.21266552 doi: medRxiv preprint F i g u r e 2 . N e u t r a l i z i n g t i t e r s o f B N T 1 6 2 b 2 v a c c i n a t e d v o l u n t e e r s a g a i n s t M u , G a m m a , a n d B . 1 . 1 1 1 S A R S -C o v -2 i s o l a t e s . T C I D 5 0 -b a s e d a s s a y s w e r e p e r f o r m e d b y i n c u b a t i n g 1 2 0 T C D I 5 0 o f e a c h S A R S -C o V -2 i s o l a t e w i t h f i v e 2 -f o l d s e r i a l d i l u t i o n s o f s e r a f r o m B N T 1 6 2 b 2 v a c c i n a t e d v o l u n t e e r s . T h i n c r e a s e i n t h e n u m b e r o f c a s e s o f t h e t h i r d e p i d e m i o l o g i c a l p e a k i n C o l o m b i a , a l t h o u g h t h e g r e a t e r r e p r e s e n t a t i v e n e s s o f M u p o t e n t i a l l y i m p l i e s a g r e a t e r e p i d e m i o l o g i c a l i m p a c t o f t h i s v a r i a n t ( F i g . 1 ) . I n t h i s s t u d y , a 3 . 4 -f o l d d e c r e a s e i n t h e n e u t r a l i z a t i o n o f G a m m a r e l a t i v e t o B . 1 . 1 1 1 v a r i a n t w a . CC-BY-NC-ND 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) preprint The copyright holder for this this version posted November 19, 2021. ; https://doi.org/10.1101/2021.11.19.21266552 doi: medRxiv preprint Emerging Variants of SARS-CoV-2 And Novel Therapeutics Against Coronavirus (COVID-19) WHO, Tracking SARS-CoV-2 variants Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2 Ineffective neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine sera A cluster of the new SARS-CoV-2 B.1.621 lineage in Italy and sensitivity of the viral isolate to the BNT162b2 vaccine Alexander Casas Castro;, Estrategia de caracterización genómica por muestreo probabilístico para SARS-CoV-2 en Colombia: Primer muestreo 2403 Establishment of the WHO International Standard and Reference Panel for anti-SARS-CoV-2 antibody SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies Ineffective neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine sera Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K Funding The authors thank the study participants for their dedication, the National Laboratory Network for routine virologic surveillance of SARS-CoV-2 in Colombia. We also thank all This work was funded by the Instituto Nacional de Salud project code CEMIN-04-2021 and Sistema General de Regalías (SGR) project code BPIN 2020000100151. No conflict of interest was reported by the authors. The study protocol was approved by the Ethics Committee of the Colombian National Health Institute, (CEMIN)-04-2021, carried out in accordance with the Declaration of Helsinki. All subjects enrolled in this research responded voluntarily to an informed consent formulary.