tetano
Editor, Senior Moderator
Cell
. 2021 Dec 3;S0092-8674(21)01405-7.
doi: 10.1016/j.cell.2021.12.002. Online ahead of print.
Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung
Matthew Gagne[SUP] 1 [/SUP], Kizzmekia S Corbett[SUP] 1 [/SUP], Barbara J Flynn[SUP] 1 [/SUP], Kathryn E Foulds[SUP] 1 [/SUP], Danielle A Wagner[SUP] 1 [/SUP], Shayne F Andrew[SUP] 1 [/SUP], John-Paul M Todd[SUP] 1 [/SUP], Christopher Cole Honeycutt[SUP] 1 [/SUP], Lauren McCormick[SUP] 1 [/SUP], Saule T Nurmukhambetova[SUP] 1 [/SUP], Meredith E Davis-Gardner[SUP] 2 [/SUP], Laurent Pessaint[SUP] 3 [/SUP], Kevin W Bock[SUP] 4 [/SUP], Bianca M Nagata[SUP] 4 [/SUP], Mahnaz Minai[SUP] 4 [/SUP], Anne P Werner[SUP] 1 [/SUP], Juan I Moliva[SUP] 1 [/SUP], Courtney Tucker[SUP] 1 [/SUP], Cynthia G Lorang[SUP] 1 [/SUP], Bingchun Zhao[SUP] 1 [/SUP], Elizabeth McCarthy[SUP] 1 [/SUP], Anthony Cook[SUP] 3 [/SUP], Alan Dodson[SUP] 3 [/SUP], I-Ting Teng[SUP] 1 [/SUP], Prakriti Mudvari[SUP] 1 [/SUP], Jesmine Roberts-Torres[SUP] 1 [/SUP], Farida Laboune[SUP] 1 [/SUP], Lingshu Wang[SUP] 1 [/SUP], Adrienne Goode[SUP] 3 [/SUP], Swagata Kar[SUP] 3 [/SUP], Seyhan Boyoglu-Barnum[SUP] 1 [/SUP], Eun Sung Yang[SUP] 1 [/SUP], Wei Shi[SUP] 1 [/SUP], Aurélie Ploquin[SUP] 1 [/SUP], Nicole Doria-Rose[SUP] 1 [/SUP], Andrea Carfi[SUP] 5 [/SUP], John R Mascola[SUP] 1 [/SUP], Eli A Boritz[SUP] 1 [/SUP], Darin K Edwards[SUP] 5 [/SUP], Hanne Andersen[SUP] 3 [/SUP], Mark G Lewis[SUP] 3 [/SUP], Mehul S Suthar[SUP] 2 [/SUP], Barney S Graham[SUP] 1 [/SUP], Mario Roederer[SUP] 1 [/SUP], Ian N Moore[SUP] 4 [/SUP], Martha C Nason[SUP] 6 [/SUP], Nancy J Sullivan[SUP] 1 [/SUP], Daniel C Douek[SUP] 7 [/SUP], Robert A Seder[SUP] 8 [/SUP]
Affiliations
Abstract
mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID[SUB]50[/SUB] at weeks 6 (peak) and 48 (challenge), respectively. Antibody-binding titers also decreased in bronchoalveolar lavage (BAL). Four days after Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by ∼3-log[SUB]10[/SUB] compared with control animals. In nasal swabs, sgRNA was reduced by 1-log[SUB]10[/SUB], and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.
Keywords: B cells; COVID-19; Delta; SARS-CoV-2; T cells; anamnestic; antibody; mRNA vaccine; mucosal immunity; nonhuman primates.
. 2021 Dec 3;S0092-8674(21)01405-7.
doi: 10.1016/j.cell.2021.12.002. Online ahead of print.
Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung
Matthew Gagne[SUP] 1 [/SUP], Kizzmekia S Corbett[SUP] 1 [/SUP], Barbara J Flynn[SUP] 1 [/SUP], Kathryn E Foulds[SUP] 1 [/SUP], Danielle A Wagner[SUP] 1 [/SUP], Shayne F Andrew[SUP] 1 [/SUP], John-Paul M Todd[SUP] 1 [/SUP], Christopher Cole Honeycutt[SUP] 1 [/SUP], Lauren McCormick[SUP] 1 [/SUP], Saule T Nurmukhambetova[SUP] 1 [/SUP], Meredith E Davis-Gardner[SUP] 2 [/SUP], Laurent Pessaint[SUP] 3 [/SUP], Kevin W Bock[SUP] 4 [/SUP], Bianca M Nagata[SUP] 4 [/SUP], Mahnaz Minai[SUP] 4 [/SUP], Anne P Werner[SUP] 1 [/SUP], Juan I Moliva[SUP] 1 [/SUP], Courtney Tucker[SUP] 1 [/SUP], Cynthia G Lorang[SUP] 1 [/SUP], Bingchun Zhao[SUP] 1 [/SUP], Elizabeth McCarthy[SUP] 1 [/SUP], Anthony Cook[SUP] 3 [/SUP], Alan Dodson[SUP] 3 [/SUP], I-Ting Teng[SUP] 1 [/SUP], Prakriti Mudvari[SUP] 1 [/SUP], Jesmine Roberts-Torres[SUP] 1 [/SUP], Farida Laboune[SUP] 1 [/SUP], Lingshu Wang[SUP] 1 [/SUP], Adrienne Goode[SUP] 3 [/SUP], Swagata Kar[SUP] 3 [/SUP], Seyhan Boyoglu-Barnum[SUP] 1 [/SUP], Eun Sung Yang[SUP] 1 [/SUP], Wei Shi[SUP] 1 [/SUP], Aurélie Ploquin[SUP] 1 [/SUP], Nicole Doria-Rose[SUP] 1 [/SUP], Andrea Carfi[SUP] 5 [/SUP], John R Mascola[SUP] 1 [/SUP], Eli A Boritz[SUP] 1 [/SUP], Darin K Edwards[SUP] 5 [/SUP], Hanne Andersen[SUP] 3 [/SUP], Mark G Lewis[SUP] 3 [/SUP], Mehul S Suthar[SUP] 2 [/SUP], Barney S Graham[SUP] 1 [/SUP], Mario Roederer[SUP] 1 [/SUP], Ian N Moore[SUP] 4 [/SUP], Martha C Nason[SUP] 6 [/SUP], Nancy J Sullivan[SUP] 1 [/SUP], Daniel C Douek[SUP] 7 [/SUP], Robert A Seder[SUP] 8 [/SUP]
Affiliations
- PMID: 34921774
- DOI: 10.1016/j.cell.2021.12.002
Abstract
mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID[SUB]50[/SUB] at weeks 6 (peak) and 48 (challenge), respectively. Antibody-binding titers also decreased in bronchoalveolar lavage (BAL). Four days after Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by ∼3-log[SUB]10[/SUB] compared with control animals. In nasal swabs, sgRNA was reduced by 1-log[SUB]10[/SUB], and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.
Keywords: B cells; COVID-19; Delta; SARS-CoV-2; T cells; anamnestic; antibody; mRNA vaccine; mucosal immunity; nonhuman primates.