A5050833058- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- Animal Virus Infections Studies
- Immunotherapy and Immune Responses
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Long-Term Effects of COVID-19
- T-cell and B-cell Immunology
- Mosquito-borne diseases and control
- Bacillus and Francisella bacterial research
- Viral Infections and Vectors
- Malaria Research and Control
- Viral Infections and Immunology Research
- COVID-19 Impact on Reproduction
- Vaccine Coverage and Hesitancy
- Viral Infections and Outbreaks Research
- CAR-T cell therapy research
Icahn School of Medicine at Mount Sinai
2024
Rockefeller University
2020-2023
Abstract More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) remains difficult to control despite availability of several working vaccines. Progress in controlling is slowed emergence variants that appear be more transmissible and resistant antibodies 1,2 . Here we report on a cohort 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 12 months SARS-CoV-2 infection, 41% whom also...
The emergence of SARS-CoV-2 and the ensuing explosive epidemic COVID-19 disease has generated a need for assays to rapidly conveniently measure antiviral activity SARS-CoV-2–specific antibodies. Here, we describe collection approaches based on spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1), vesicular stomatitis (VSV), as well replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate exhibited subtle differences in...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B cell responses that continue to evolve for at least a year. During time, memory cells express increasingly broad and potent antibodies are resistant mutations found in variants of concern 1 . As result, vaccination disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines high levels plasma neutralizing activity against all tested 1,2 Here we examine evolution five months...
The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals
SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal (NTD) of spike trimer (S) constitute two major targets for antibodies. Here, we use NTD-specific probes capture anti-NTD memory B cells in a longitudinal cohort infected individuals, some whom were vaccinated. We found 6 complementation groups 58% targeted epitopes outside NTD supersite, neutralized either Gamma...
The Omicron SARS-CoV-2 variant has spread internationally and is responsible for rapidly increasing case numbers. emergence of divergent variants in the context a heterogeneous evolving neutralizing antibody response host populations might compromise protection afforded by vaccines or prior infection. We measured titers 169 longitudinally collected plasma samples using pseudotypes bearing Wuhan-hu-1 laboratory-designed neutralization-resistant spike (PMS20). Plasmas were obtained from...
Abstract The emergence of SARS-CoV-2 and the ensuing explosive epidemic COVID19 disease has generated a need for assays to rapidly conveniently measure antiviral activity SARS-CoV-2-specific antibodies. Here, we describe collection approaches based on spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1) vesicular stomatitis (VSV), as well replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate exhibited subtle differences in...
Individuals who receive a third mRNA vaccine dose show enhanced protection against severe COVID-19, but little is known about the impact of breakthrough infections on memory responses. Here, we examine antibodies that develop after or fourth antigenic exposure by Delta Omicron BA.1 infection, respectively. A to antigen increases number B cells produce with comparable potency and breadth dose. infection increased variant-specific plasma antibody cell However, did not increase overall...
The omicron variant of SARS-CoV-2 infected very large numbers vaccinated and convalescent individuals 1-3 . penetrance this in the antigen experienced human population can be explained part by relatively low levels plasma neutralizing activity against Omicron people who were or with original Wuhan-Hu-1 strain 4-7 3 rd mRNA vaccine dose produces an initial increase circulating anti-Omicron antibodies, but titers remain 10-20-fold lower than are, many cases, insufficient to prevent infection 7...
Over one year after its inception, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains difficult to control despite availability of several excellent vaccines. Progress in controlling is slowed emergence variants that appear be more transmissible and resistant antibodies 1,2 . Here we report on a cohort 63 COVID-19-convalescent individuals assessed at 1.3, 6.2 12 months infection, 41% whom also received mRNA vaccines...
The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale pace. As result, current regimens comprise diverse vaccine modalities, immunogen combinations, dosing intervals. Here, we compare vaccine-specific antibody memory B cell responses following two-dose mRNA, single-dose Ad26.COV.2S, ChAdOx1, or combination ChAdOx1/mRNA vaccination. Plasma-neutralizing activity, as well magnitude, clonal composition, maturation...
The number and variability of the neutralizing epitopes targeted by polyclonal antibodies in SARS-CoV-2 convalescent vaccinated individuals are key determinants neutralization breadth and, consequently, genetic barrier to viral escape. Using chimeric viruses antibody-selected mutants, we show that multiple epitopes, within outside receptor binding domain (RBD), variably plasma coincide with sequences enriched for diversity natural populations. By combining plasma-selected spike...
The single-dose Ad.26.COV.2 (Janssen) vaccine elicits lower levels of neutralizing antibodies and shows more limited efficacy in protection against infection than either the two available mRNA vaccines. In addition, has been less effective severe disease during Omicron surge. Here, we examined memory B cell response to vaccination. Compared with vaccines, recipients had significantly numbers RBD-specific cells 1.5 or 6 mo after Despite numbers, overall quality responses appears be similar,...
Abstract Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host response is required for viremia pathogenesis in vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized mice infectable. Here, we explore how evolution impacts antagonism. By measuring susceptibility 38 diverse proteins, demonstrate that arose numerous times mammalian...
Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least one year. During time, memory B cells express increasingly broad and potent antibodies are resistant mutations found in variants of concern 1 . As a result, vaccination disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines high levels plasma neutralizing activity against all tested 1, Here, we examine cell evolution 5...
Abstract The effects of heterogeneous infection, vaccination and boosting histories prior to during pregnancy have not been extensively studied are likely important for protection neonates. We measure levels spike binding antibodies in 4600 patients their neonates with different statuses, without history SARS-CoV-2 infection. investigate neutralizing antibody activity against variant pseudotypes a subset 259 determined correlation between IgG activity. further study the ability maternal...
Global population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accumulating through heterogeneous combinations of infection and vaccination. Vaccine distribution in low- middle-income countries has been variable reliant on diverse vaccine platforms. We studied B-cell Mexico, a country where five different vaccines have deployed populations with high SARS-CoV-2 incidences. Levels antibodies that bound stabilized prefusion spike trimer, neutralizing antibody...
SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor binding domain (RBD) and the N-terminal (NTD) of spike trimer (S) constitute two major targets for system. Neutralizing antibodies targeting RBD bind several different sites on this domain. In contrast, most NTD characterized date a single supersite, however these were obtained by methods not specific. Here we use specific probes focus anti-NTD memory B cells...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global problem in part because of the emergence variants concern that evade neutralization by antibodies elicited prior infection or vaccination. Here we report on human neutralizing antibody and memory responses Gamma variant cohort hospitalized individuals. Plasma from infected individuals potently neutralized viruses pseudotyped with SARS-CoV-2 spike protein, but activity against Wuhan-Hu-1-1, Beta, Delta,...
The emergence of severe acute respiratory syndrome coronavirus 2 variants that have greater transmissibility and resistance to neutralizing antibodies has increased the incidence breakthrough infections. We show infection increases antibody titers varying degrees depending on nature variant number vaccine doses previously administered. Omicron resulted in were highest across all groups, particularly against Omicron.
Abstract Individuals that receive a 3 rd mRNA vaccine dose show enhanced protection against severe COVID19 but little is known about the impact of breakthrough infections on memory responses. Here, we examine antibodies develop after or 4 th antigenic exposure by Delta Omicron BA.1 infection, respectively. A to antigen increases number B cells produce with comparable potency and breadth dose. infection increased variant specific plasma antibody cell However, did not increase overall...