Correlates of protection against SARS-CoV-2 infection and COVID-19 disease

Antibodies against epitopes in S1 give the most accurate CoP against infection by the SARS-CoV-2 coronavirus. Measurement of those antibodies by neutralization or binding assays both have predictive value, with binding antibody titers giving the highest statistical correlation. However, the protective functions of antibodies are multiple. Antibodies with multiple functions other than neutralization influence efficacy. The role of cellular responses can be discerned with respect to CD4+ T cells and their augmentation of antibodies, and with respect to CD8+ cells with regard to control of viral replication, particularly in the presence of insufficient antibody. More information is needed on mucosal responses

Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration.

Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance

Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines

Funding Information: We thank Nancy Zimmerman, Mark and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for support. We acknowledge support from the Ragon Institute of Mass General, MIT, and Harvard (to G.A.) the Massachusetts Consortium on Pathogen Readiness (MassCPR) (to G.A.), and the National Institutes of Health ( 3R37AI080289-11S1 , R01AI146785 , U19AI42790–01 , U19AI135995–02 , U19AI42790-01 , 1U01CA260476 – 01 , and CIVIC75N93019C00052 ) (to G.A.). Publisher Copyright: © 2023Despite the successes of current coronavirus disease 2019 (COVID-19) vaccines, waning immunity, the emergence of variants of concern, and breakthrough infections among vaccinees have begun to highlight opportunities to improve vaccine platforms. Real-world vaccine efficacy studies have highlighted the reduced risk of breakthrough infections and diseases among individuals infected and vaccinated, referred to as hybrid immunity. Thus, we sought to define whether hybrid immunity shapes the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following Pfizer/BNT162b2, Moderna mRNA-1273, ChadOx1/AZD1222, and Ad26.COV2.S vaccination. Each vaccine exhibits a unique functional humoral profile in vaccination only or hybrid immunity. However, hybrid immunity shows a unique augmentation of S2-domain-specific functional immunity that was poorly induced for the vaccination only. These data highlight the importance of natural infection in breaking the immunodominance away from the evolutionarily unstable S1 domain and potentially affording enhanced cross-variant protection by targeting the more highly conserved S2 domain of SARS-CoV-2.publishersversionPeer reviewe

Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines

Despite the successes of current coronavirus disease 2019 (COVID-19) vaccines, waning immunity, the emergence of variants of concern, and breakthrough infections among vaccinees have begun to highlight opportunities to improve vaccine platforms. Real-world vaccine efficacy studies have highlighted the reduced risk of breakthrough infections and diseases among individuals infected and vaccinated, referred to as hybrid immunity. Thus, we sought to define whether hybrid immunity shapes the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following Pfizer/BNT162b2, Moderna mRNA-1273, ChadOx1/AZD1222, and Ad26.COV2.S vaccination. Each vaccine exhibits a unique functional humoral profile in vaccination only or hybrid immunity. However, hybrid immunity shows a unique augmentation of S2-domain-specific functional immunity that was poorly induced for the vaccination only. These data highlight the importance of natural infection in breaking the immunodominance away from the evolutionarily unstable S1 domain and potentially affording enhanced cross-variant protection by targeting the more highly conserved S2 domain of SARS-CoV-2

Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci

Streptococcus pneumoniae (pneumococcus) is a nasopharyngeal commensal and respiratory pathogen. This study characterises the immunoglobulin G (IgG) repertoire recognising pneumococci from birth to 24 months old (mo) in a prospectively-sampled cohort of 63 children using a panproteome array. IgG levels are highest at birth, due to transplacental transmission of maternal antibodies. The subsequent emergence of responses to individual antigens exhibit distinct kinetics across the cohort. Stable differences in the strength of individuals’ responses, correlating with maternal IgG concentrations, are established by 6 mo. By 12 mo, children develop unique antibody profiles that are boosted by re-exposure. However, some proteins only stimulate substantial responses in adults. Integrating genomic data on nasopharyngeal colonisation demonstrates rare pneumococcal antigens can elicit strong IgG levels post-exposure. Quantifying such responses to the diverse core loci (DCL) proteins is complicated by cross-immunity between variants. In particular, the conserved N terminus of DCL protein zinc metalloprotease B provokes the strongest early IgG responses. DCL proteins’ ability to inhibit mucosal immunity likely explains continued pneumococcal carriage despite hosts’ polyvalent antibody repertoire. Yet higher IgG levels are associated with reduced incidence, and severity, of pneumonia, demonstrating the importance of the heterogeneity in response strength and kinetics across antigens and individuals

Genomics Reveals the Worldwide Distribution of Multidrug-Resistant Serotype 6E Pneumococci.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The pneumococcus is a leading pathogen infecting children and adults. Safe, effective vaccines exist, and they work by inducing antibodies to the polysaccharide capsule (unique for each serotype) that surrounds the cell; however, current vaccines are limited by the fact that only a few of the nearly 100 antigenically distinct serotypes are included in the formulations. Within the serotypes, serogroup 6 pneumococci are a frequent cause of serious disease and common colonizers of the nasopharynx in children. Serotype 6E was first reported in 2004 but was thought to be rare; however, we and others have detected serotype 6E among recent pneumococcal collections. Therefore, we analyzed a diverse data set of ∼1,000 serogroup 6 genomes, assessed the prevalence and distribution of serotype 6E, analyzed the genetic diversity among serogroup 6 pneumococci, and investigated whether pneumococcal conjugate vaccine-induced serotype 6A and 6B antibodies mediate the killing of serotype 6E pneumococci. We found that 43% of all genomes were of serotype 6E, and they were recovered worldwide from healthy children and patients of all ages with pneumococcal disease. Four genetic lineages, three of which were multidrug resistant, described ∼90% of the serotype 6E pneumococci. Serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to elicit killing of serotype 6E pneumococci. We also revealed three major genetic clusters of serotype 6A capsular sequences, discovered a new hybrid 6C/6E serotype, and identified 44 examples of serotype switching. Therefore, while vaccines appear to offer protection against serotype 6E, genetic variants may reduce vaccine efficacy in the longer term because of the emergence of serotypes that can evade vaccine-induced immunity

Exile Vol. XXIII No. 2

PROSE The End of East by Libby Thomas 3-12 Lilt by Andrew Calabrese 13 The Egg Lady by Nancy Jones 14-20 The International Man by Chip Finefrock 21-31 MUSIC Theme and Variations Op.2, No 1. by J. J. Fuerst 32-38 POETRY Thrown Out Of The Game by Herberto Padilla to Yannis Ritzos in a Greek jail (Translated from the Spanish by José de Armas) 39 Plumb-Creek In Late Sunlight by Lenore Mayhew 40 untitled by Sharon Singleton 41 untitled by Sharon Singleton 42 A Dance Of Stones by Lawrence Weber 43-44 Carp and Crane by William McNaughton 45 Mountain Ash by Dawn Patnode 46-49 untitled by Mary de Rachewiltz 50 Kai Gar Onar Ek Dios Estin by William McNaughton 51 acute angles by Gay Parks 52 Annihilating All Made To A Thought by Tony Stoneburner 53 Dead Fish by Deneise Deter 54 Changing by Deb Allbery 54 Finish Lines by David A. Goldblatt 55 Malinche\u27s Sister by Tona Dickerson 56 Tarde en el hospital by Carlos Peoza Veliz 57 Afternoon in the Hospital by Carlos Peoza Veliz (Tanslated from the Spanish by Joan Straub) 57 Cuadrados Y Angulos by Alfonaina Storni 58 Squares and Angles by Alfonaina Storni (Translated from the Spanish by Joan Straub) 58 INK DRAWINGS untitled by Susan Hoagman 2 Self-Portrait or Darla by Julia Weatherford 59 untitled by Katy Booth 70 ESSAYS On As For Poets by Gary Snyder 60-61 Joseph Heller\u27s Something Happened and the Problem of Community in Modern America by Jack Kirby 62-68 EDITOR\u27S NOTE by Lawrence Weber 69-70 CONTRIBUTORS 71-72 The cover ink drawing by Cathy Ries is entitled, Exercise In Exaggerated Contours

When to update COVID-19 vaccine composition

Vaccines against different SARS-CoV-2 variants have been approved, but continued surveillance is needed to determine when the antigen composition of vaccines should be updated, together with clinical studies to assess vaccine efficacy

Action on the social determinants for advancing health equity in the time of COVID-19: perspectives of actors engaged in a WHO Special Initiative.

Since the 2008 publication of the reports of the Commission on Social Determinants of Health and its nine knowledge networks, substantial research has been undertaken to document and describe health inequities. The COVID-19 pandemic has underscored the need for a deeper understanding of, and broader action on, the social determinants of health. Building on this unique and critical opportunity, the World Health Organization is steering a multi-country Initiative to reduce health inequities through an action-learning process in 'Pathfinder' countries. The Initiative aims to develop replicable and reliable models and practices that can be adopted by WHO offices and UN staff to address the social determinants of health to advance health equity. This paper provides an overview of the Initiative by describing its broad theory of change and work undertaken in three regions and six Pathfinder countries in its first year-and-a-half. Participants engaged in the Initiative describe results of early country dialogues and promising entry points for implementation that involve model, network and capacity building. The insights communicated through this note from the field will be of interest for others aiming to advance health equity through taking action on the social determinants of health, in particular as regards structural determinants