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1.
Nature ; 2021 Dec 31.
Article in English | MEDLINE | ID: covidwho-1616995

ABSTRACT

The Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in November of 2021 in South Africa and Botswana as well as in a sample from a traveler from South Africa in Hong Kong1,2. Since then, B.1.1.529 has been detected globally. This variant seems to be at least equally infectious than B.1.617.2 (Delta), has already caused super spreader events3 and has outcompeted Delta within weeks in several countries and metropolitan areas. B.1.1.529 hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness2,4-6. Here, we investigated the neutralizing and binding activity of sera from convalescent, mRNA double vaccinated, mRNA boosted, convalescent double vaccinated, and convalescent boosted individuals against wild type, B.1.351 and B.1.1.529 SARS-CoV-2 isolates. Neutralizing activity of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529 while neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at significantly reduced levels. Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated individuals, but was mostly retained in vaccinated individuals.

2.
Preprint | EuropePMC | ID: ppcovidwho-296962

ABSTRACT

Mucosal immune responses are critical to prevent respiratory infections but it is unclear to what extent antigen specific mucosal secretory IgA (SIgA) antibodies are induced by mRNA vaccination in humans. We analyzed, therefore, paired serum and saliva samples from study participants with and without COVID-19 at multiple timepoints before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Our results suggest that the level of mucosal SIgA responses induced by mRNA vaccination depend on pre-existing immunity. Indeed, vaccination induced only a weak mucosal SIgA response in individuals without pre-existing mucosal antibody responses to SARS-CoV-2 while SIgA induction after vaccination was efficient in COVID-19 survivors. Our data indicate that vaccinated seropositive individuals were able to swiftly induce relatively high anti-spike SIgA responses by boosting pre-existing mucosal immunity. In contrast, seronegative individuals did not have pre-existing anti-SARS-CoV-2 or cross-reacting anti-HCoV SIgA antibodies prior to vaccination, and, thus, little or no anti-SARS-CoV-2 SIgA antibodies were induced by vaccination in these individuals.

3.
Preprint in English | Other preprints | ID: ppcovidwho-294083

ABSTRACT

Summary In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.

7.
EBioMedicine ; 73: 103626, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1471943

ABSTRACT

BACKGROUND: Highly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning. Several of these viral variants have the potential to partially escape neutralizing antibody responses, warranting continued immune-monitoring. METHODS: We used a panel of 30 post-mRNA vaccination sera to determine neutralization and RBD and spike binding activity against a number of emerging viral variants. The virus neutralization was determined using authentic SARS-CoV-2 clinical isolates in an assay format that mimics physiological conditions. FINDINGS: We tested seven currently circulating viral variants of concern/interest, including the three Iota sublineages, Alpha (E484K), Beta, Delta and Lambda in neutralization assays. We found only small decreases in neutralization against Iota and Delta. The reduction was stronger against a sub-variant of Lambda, followed by Beta and Alpha (E484K). Lambda is currently circulating in parts of Latin America and was detected in Germany, the US and Israel. Of note, reduction in a receptor binding domain and spike binding assay that also included Gamma, Kappa and A.23.1 was negligible. INTERPRETATION: Taken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity. FUNDING: This work is part of the PARIS/SPARTA studies funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. In addition, this work was also partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384), by anonymous donors and by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003.

9.
Cell ; 184(15): 3936-3948.e10, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1260677

ABSTRACT

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to spikes of seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine-induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , RNA, Messenger/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Neutralizing/immunology , Antibody Formation/immunology , Binding, Competitive , Humans , Immunoglobulin G/metabolism , Mutation/genetics , Protein Domains , Somatic Hypermutation, Immunoglobulin/genetics
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