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  • 1
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 377, No. 6603 ( 2022-07-15)
    Abstract: B.1.1.529 (Omicron) and its subvariants pose new challenges for control of the COVID-19 pandemic. Although vaccinated populations are relatively protected from severe disease and death, countries with high vaccine uptake are experiencing substantial caseloads with breakthrough infection and frequent reinfection. RATIONALE We analyzed cross-protective immunity against B.1.1.529 (Omicron) in triple-vaccinated health care workers (HCWs) with different immune-imprinted histories of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the ancestral Wuhan Hu-1, B.1.1.7 (Alpha), and B.1.617.2 (Delta) waves and after infection during the B.1.1.529 (Omicron) wave in previously infection-naïve individuals and those with hybrid immunity, to investigate whether B.1.1.529 (Omicron) infection could further boost adaptive immunity. Spike subunit 1 (S1) receptor binding domain (RBD) and whole spike binding, live virus neutralizing antibody (nAb) potency, memory B cell (MBC) frequency, and T cell responses against peptide pools and naturally processed antigen were assessed. RESULTS B and T cell recognition and nAb potency were boosted against previous variants of concern (VOCs) in triple-vaccinated HCWs, but this enhanced immunity was attenuated against B.1.1.529 (Omicron) itself. Furthermore, immune imprinting after B.1.1.7 (Alpha) infection resulted in reduced durability of antibody binding against B.1.1.529 (Omicron), and S1 RBD and whole spike VOC binding correlated poorly with live virus nAb potency. Half of triple-vaccinated HCWs showed no T cell response to B.1.1.529 (Omicron) S1 processed antigen, and all showed reduced responses to the B.1.1.529 (Omicron) peptide pool, irrespective of SARS-CoV-2 infection history. Mapping T cell immunity in class II human leukocyte antigen transgenics showed that individual spike mutations could result in loss or gain of T cell epitope recognition, with changes to T cell effector and regulatory programs. Triple-vaccinated, previously infection-naïve individuals infected during the B.1.1.529 (Omicron) wave showed boosted cross-reactive S1 RBD and whole spike binding, live virus nAb potency, and T cell immunity against previous VOCs but less so against B.1.1.529 (Omicron) itself. Immune imprinting from prior Wuhan Hu-1 infection abrogated any enhanced cross-reactive antibody binding, T cell recognition, MBC frequency, or nAb potency after B.1.1.529 (Omicron) infection. CONCLUSION Vaccine boosting results in distinct, imprinted patterns of hybrid immunity with different combinations of SARS-CoV-2 infection and vaccination. Immune protection is boosted by B.1.1.529 (Omicron) infection in the triple-vaccinated, previously infection-naïve individuals, but this boosting is lost with prior Wuhan Hu-1 imprinting. This “hybrid immune damping” indicates substantial subversion of immune recognition and differential modulation through immune imprinting and may be the reason why the B.1.1.529 (Omicron) wave has been characterized by breakthrough infection and frequent reinfection with relatively preserved protection against severe disease in triple-vaccinated individuals. Hybrid immune damping. ( A ) Triple-vaccinated HCWs with different SARS-CoV-2 infection histories show boosted cross-reactive immunity against VOCs, less so against Omicron. ( B ) Breakthrough infection during the Omicron wave boosts cross-reactive immunity in triple-vaccinated, previously infection-naïve individuals against VOCs, less so against Omicron itself; imprinting by previous Wuhan Hu-1 infection ablates Omicron immune boosting. ( C ) T cell recognition of Omicron mutation sequences is linked to altered transcription.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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  • 2
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 372, No. 6549 ( 2021-06-25), p. 1418-1423
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine rollout has coincided with the spread of variants of concern. We investigated whether single-dose vaccination, with or without prior infection, confers cross-protective immunity to variants. We analyzed T and B cell responses after first-dose vaccination with the Pfizer/BioNTech messenger RNA vaccine BNT162b2 in health care workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody-secreting memory B cell response to the spike protein, and neutralizing antibodies effective against variants B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated, or unchanged T cell responses, depending on human leukocyte antigen (HLA) polymorphisms. Single-dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
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  • 3
    In: English Studies, Informa UK Limited, Vol. 47, No. 1-6 ( 1966-01), p. 27-442
    Type of Medium: Online Resource
    ISSN: 0013-838X , 1744-4217
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    Language: English
    Publisher: Informa UK Limited
    Publication Date: 1966
    detail.hit.zdb_id: 2007175-9
    SSG: 7,24
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  • 4
    In: English Studies, Informa UK Limited, Vol. 47, No. 1-6 ( 1966-01), p. 47-467
    Type of Medium: Online Resource
    ISSN: 0013-838X , 1744-4217
    RVK:
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 1966
    detail.hit.zdb_id: 2007175-9
    SSG: 7,24
    Location Call Number Limitation Availability
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  • 5
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 381, No. 6657 ( 2023-08-04)
    Abstract: Genetic analysis of historical individuals has the potential to help restore knowledge of people whose stories were omitted from written records. During the late 18th and early 19th centuries, Catoctin Furnace in Maryland relied on a workforce of enslaved individuals to operate the iron furnace and carry out domestic and agricultural tasks. Despite the role that Catoctin Furnace played in early US history (including supplying munitions during the Revolutionary War), relatively little is known about the African Americans who labored there or their descendants compared with the furnace’s later, predominantly white workforce. RATIONALE We produced genome-wide data for 27 individuals buried in the Catoctin Furnace African American Cemetery and compared them to ~9.3 million consenting research participants genotyped by 23andMe, Inc., to address the following questions: (i) How were the Catoctin individuals related to each other? (ii) What were the sources of their African and European ancestry? (iii) Where in the US do their genetic relatives live today, including their direct descendants? (iv) What can their genomes reveal about their health? RESULTS We identified five genetic families, consisting of biological mothers, children, and siblings, among the Catoctin individuals. In most cases, biological family members were buried in close proximity. All but one of the Catoctin individuals had primarily African ancestry, with variable amounts of European ancestry. To learn more about their ancestry, we developed an approach to detect identical-by-descent segments of the genome shared between the Catoctin individuals and 23andMe research participants. Identical-by-descent segments of DNA are shared by two or more people because they have been inherited from a recent common ancestor. We identified 41,799 close and distant relatives of the Catoctin individuals among 23andMe research participants. Within Africa, we found the highest rates of genetic sharing between Catoctin individuals and research participants who self-identified as belonging to the Wolof or Kongo ethnolinguistic groups. Within Europe, we observed the highest rates of genetic sharing with research participants that have ties to Great Britain and Ireland. Within the US, participants from the South showed elevated rates of sharing, largely reflecting distant connections to 23andMe research participants with sub-Saharan African ancestry (possibly tracing back to shared common ancestors in Africa). When we considered genetic relatives who share the most identical DNA with the Catoctin individuals, we observed the highest rates of sharing in Maryland, suggesting that at least some descendants stayed in the region after the furnace’s transition away from enslaved and paid African American labor. Finally, we found that some of the Catoctin individuals carried risk factors for sickle cell anemia and glucose-6-phosphate dehydrogenase deficiency, genetic diseases that are common in African Americans today. CONCLUSION These results demonstrate the power of joint analysis of DNA from historical individuals and the extremely large datasets generated through direct-to-consumer ancestry testing, and they serve as a model for obtaining direct insights into the genome-wide genetic ancestry of enslaved people in the historical US. Genetic connections to individuals from Catoctin Furnace African American Cemetery in Maryland. A timeline highlighting major events in the history of Catoctin Furnace and the birth years of research participants in the 23andMe cohort, presented alongside maps showing the proportion of 23andMe research participants associated with geographic coordinates in the US, sub-Saharan Africa, and Europe who share genetic connections to the Catoctin individuals.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
    Location Call Number Limitation Availability
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