Comprehensive characterization of stemness-related lncRNAs in triple-negative breast cancer identified a novel prognostic signature related to treatment outcomes, immune landscape analysis and therapeutic guidance: a silico analysis with in vivo experiments.

BACKGROUND: Cancer stem cells (CSCs) and long non-coding RNAs (lncRNAs) are known to play a crucial role in the growth, migration, recurrence, and drug resistance of tumor cells, particularly in triple-negative breast cancer (TNBC). This study aims to investigate stemness-related lncRNAs (SRlncRNAs) as potential prognostic indicators for TNBC patients. METHODS: Utilizing RNA sequencing data and corresponding clinical information from the TCGA database, and employing Weighted Gene Co-expression Network Analysis (WGCNA) on TNBC mRNAsi sourced from an online database, stemness-related genes (SRGs) and SRlncRNAs were identified. A prognostic model was developed using univariate Cox and LASSO-Cox analysis based on SRlncRNAs. The performance of the model was evaluated using Kaplan-Meier analysis, ROC curves, and ROC-AUC. Additionally, the study delved into the underlying signaling pathways and immune status associated with the divergent prognoses of TNBC patients. RESULTS: The research identified a signature of six SRlncRNAs (AC245100.6, LINC02511, AC092431.1, FRGCA, EMSLR, and MIR193BHG) for TNBC. Risk scores derived from this signature were found to correlate with the abundance of plasma cells. Furthermore, the nominated chemotherapy drugs for TNBC exhibited considerable variability between different risk score groups. RT-qPCR validation confirmed abnormal expression patterns of these SRlncRNAs in TNBC stem cells, affirming the potential of the SRlncRNAs signature as a prognostic biomarker. CONCLUSION: The identified signature not only demonstrates predictive power in terms of patient outcomes but also provides insights into the underlying biology, signaling pathways, and immune status associated with TNBC prognosis. The findings suggest the possibility of guiding personalized treatments, including immune checkpoint gene therapy and chemotherapy strategies, based on the risk scores derived from the SRlncRNA signature. Overall, this research contributes valuable knowledge towards advancing precision medicine in the context of TNBC.

Zinc metabolism and its role in immunity status in subjects with trisomy 21: chromosomal dosage effect.

Introduction: Trisomy 21 (T21), which causes Down syndrome (DS), is the most common chromosomal aneuploidy in humankind and includes different clinical comorbidities, among which the alteration of the immune system has a heavy impact on patient's lives. A molecule with an important role in immune response is zinc and it is known that its concentration is significantly lower in children with T21. Different hypotheses were made about this metabolic alteration and one of the reasons might be the overexpression of superoxide dismutase 1 (SOD1) gene, as zinc is part of the SOD1 active enzymatic center. Methods: The aim of our work is to explore if there is a linear correlation between zinc level and immune cell levels measured in a total of 217 blood samples from subjects with T21. Furthermore, transcriptome map analyses were performed using Transcriptome Mapper (TRAM) software to investigate whether a difference in gene expression is detectable between subjects with T21 and euploid control group in tissues and cells involved in the immune response such as lymphoblastoid cells, thymus and white blood cells. Results: Our results have confirmed the literature data stating that the blood zinc level in subjects with T21 is lower compared to the general population; in addition, we report that the T21/control zinc concentration ratio is 2:3, consistent with a chromosomal dosage effect due to the presence of three copies of chromosome 21. The transcriptome map analyses showed an alteration of some gene's expression which might explain low levels of zinc in the blood. Discussion: Our data suggest that zinc level is not associated with the levels of immunity cells or proteins analyzed themselves and rather the main role of this ion might be played in altering immune cell function.

Ephs in cancer progression: complexity and context-dependent nature in signaling, angiogenesis and immunity.

Eph receptors constitute the largest family of receptor tyrosine kinases, comprising 14 distinct members classified into two subgroups: EphAs and EphBs.. Despite their essential functions in normal physiological processes, accumulating evidence suggests that the involvement of the Eph family in cancer is characterized by a dual and often contradictory nature. Research indicates that Eph/ephrin bidirectional signaling influences cell-cell communication, subsequently regulating cell migration, adhesion, differentiation and proliferation. The contradictory functionalities may arise from the diversity of Eph signaling pathways and the heterogeneity of different cancer microenvironment. In this review, we aim to discuss the dual role of the Eph receptors in tumor development, attempting to elucidate the paradoxical functionality through an exploration of Eph receptor signaling pathways, angiogenesis, immune responses, and more. Our objective is to provide a comprehensive understanding of the molecular mechanisms underlying tumor development. Additionally, we will explore the evolving landscape of utilizing Eph receptors as potential targets for tumor therapy and diagnostic tools.

Bulletin d'immunisation, v.46, n.1, Mar. 2024

L'Organisation panaméricaine de la santé (OPS) publie quatre fois par an le Bulletin d'Immunisation en anglais, français, portugais et espagnol. Son objectif est de faciliter l'échange d'idées et d'informations sur les programmes de vaccination dans la région des Amériques et au-delà. Il est publié depuis 1979 en anglais et en espagnol, les versions française et portugaise ayant débuté en 2001 et 2019, respectivement. Le numéro de mars 2024 du bulletin trimestriel Bulletin d'Immunisation traite des sujets suivants : Troisième réunion annuelle de la Commission régionale de suivi et de revérification de l'élimination de la rougeole, de la rubéole et du syndrome de rubéole ; Le Groupe consultatif technique de l’OPS sur les maladies évitables par la vaccination fournit des recommandations régionales sur les vaccins contre la dengue et le virus respiratoire syncytial, et publie une déclaration sur les efforts de vaccination en cours contre la COVID-19 ; Tracer la voie à suivre : réflexions sur l’initiative d’élimination des maladies transmissibles de l’OPS et les orientations futures; Vers l’élimination des maladies associées aux infections à papillomavirus humains dans la Caraïbe française : mise en œuvre d’une campagne généralisée de vaccination en milieu scolaire depuis octobre 2023; Méthodologie et outil de suivi de la performance du Programme élargi de vaccination pour la Région des Amériques; Surveillance sentinelle du rotavirus chez les enfants de moins de 5 ans dans la Région des Amériques; Surveillance sentinelle des pneumonies et méningites bactériennes chez les enfants de moins de 5 ans dans la Région des Amériques ; Atelier sur la préparation de textes et d'articles scientifiques dans le domaine de la santé à Bogota (Colombie) ; Classement final des cas, Région des Amériques, 2023 ; Le système d'information sur la vaccination et la qualité des données; Cours d'auto-apprentissage en ligne : Outils de suivi des interventions intégrées de santé publique. Vaccination et vermifugation pour la géohelminthiase ; et Renforcer la gestion des données de vaccination.

Boletim de Imunização, v.46, n.1, Mar. 2024

A Organização Pan-Americana da Saúde (OPAS) publica o Boletim de Imunização quatro vezes por ano em inglês, francês, português e espanhol. Seu objetivo é facilitar o intercâmbio de ideias e informações sobre programas de imunização na Região das Américas e fora dela. Ele é publicado desde 1979 em inglês e espanhol, com versões em francês e português iniciadas em 2001 e 2019, respectivamente. A edição de marzo de 2024 do Boletim de Imunização aborda os seguintes tópicos: Terceira Reunião Anual da Comissão Regional de Monitoramento e Reverificação da Eliminação do Sarampo, Rubéola e Síndrome da Rubéola Congênita; O Grupo Técnico Assessor da OPAS sobre Doenças Imunopreveníveis fornece recomendações regionais sobre as vacinas contra a dengue e o vírus sincicial respiratório e publica uma declaração sobre os esforços atuais de vacinação contra a COVID-19; Definição do caminho a seguir: reflexões sobre a Iniciativa da OPAS de Eliminação de Doenças Transmissíveis e orientações para o futuro; Rumo à eliminação de doenças associadas à infecção pelo papilomavírus humano no Caribe francês: implementação de uma campanha geral de vacinação nas escolas a partir de outubro de 2023; Metodologia e ferramenta de monitoramento do desempenho do Programa Ampliado de Imunização para a Região das Américas; Vigilância sentinela de rotavírus em menores de 5 anos na Região das Américas; Vigilância sentinela de casos de pneumonia e meningite bacteriana em menores de 5 anos na Região das Américas; Oficina de elaboração de textos e artigos científicos na área de saúde em Bogotá, Colômbia; Classificação final dos casos na Região das Américas, 2022; Sistema de informação de imunização e qualidade dos dados; Curso virtual de autoaprendizagem Ferramentas de monitoramento de intervenções integradas em saúde pública. Vacinação e desparasitação de geo-helmintíases; e Fortalecimento da gestão dos dados de imunização.

Immunization Newsletter, v.46, n.1, Mar. 2024

The Pan American Health Organization (PAHO) publishes the Immunization Newsletter four times a year in English, French, Portuguese, and Spanish. Its purpose is to facilitate the exchange of ideas and information on immunization programs in the Region of the Americas and beyond. It has been published since 1979 in English and Spanish, with French and Portuguese versions beginning in 2001 and 2019, respectively. The March 2024 issue of the quarterly Immunization Newsletter covers the following topics: Third annual meeting of the Regional Monitoring and Re-verification Commission for Measles, Rubella, and Congenital Rubella Syndrome Elimination; PAHO’s Technical Advisory Group (TAG) on Vaccine-preventable Diseases provides regional recommendations on dengue and respiratory syncytial virus vaccines and issues a statement on the ongoing COVID-19 vaccination efforts; Charting the path forward: reflections on PAHO's Communicable Diseases Elimination Initiative and future directions; Towards the Elimination of Diseases Associated with Human Papillomavirus Infection in the French Caribbean: Implementation of a Mass Vaccination Campaign in Schools Since October 2023; Expanded Immunization Program methodology and performance monitoring tool for the Region of the Americas; Sentinel surveillance of rotavirus in children under 5 years of age in the Region of the Americas; Sentinel surveillance of bacterial pneumonia and meningitis in children under 5 years of age in the Americas; Workshop on the preparation of scientific texts and articles on health in Bogotá, Colombia; Final Classification of Cases in the Region of the Americas, 2023; Immunization information systems and data quality; Virtual self-learning course: Tools for monitoring integrated public health interventions. Vaccination and deworming for soil-transmitted helminth infections; and Strengthening immunization data management.

Appendice. Pour une meilleure immunité : l’approche du parcours de vie pour une longévité en bonne santé

Cette publication est une annexe au document technique "Building better immunity : Une approche du parcours de vie pour une longévité en bonne santé", avec les contributions de plusieurs experts en la matière au sein et en dehors de l'Organisation panaméricaine de la santé (OPS). Cette annexe fournit des exemples d'activités au sein du programme national de vaccination qui peuvent améliorer les taux de couverture et réduire les occasions manquées pour quatre groupes de population : les femmes enceintes, les adolescents, les travailleurs de la santé et les personnes âgées. Ces exemples traduisent les principes et les concepts de l'approche fondée sur le parcours de vie en activités concrètes, qui peuvent être utilisées par les responsables des programmes nationaux de vaccination et par les vaccinateurs, respectivement, pour améliorer les taux de couverture vaccinale. Ces quatre groupes représentent des étapes de la vie pour lesquelles il existe des vaccins très efficaces et qui peuvent grandement influencer leurs capacités sanitaires. L'application des séries primaires, des rappels et des doses de vaccin de rattrapage dans ces groupes est essentielle pour combler les déficits d'immunité émergents. Les activités sont regroupées en huit composantes : (i) gestion et plaidoyer, (ii) équité, (iii) ressources humaines et financement, (iv) organisation et prestation de services, (v) génération de la demande et engagement communautaire, (vi) systèmes d'information, (vii) formation et (viii) évaluation et recherche. Les exemples doivent être évalués, adaptés, mis en œuvre et éventuellement élargis par les États membres pour s'aligner sur les contextes nationaux et locaux. Ce document s'inscrit dans le cadre des efforts déployés par l'OPS pour promouvoir l'application d'une approche de la vaccination fondée sur le parcours de vie dans les pays et territoires des Amériques et pour aider les ministères de la santé à mettre en place des stratégies de santé publique aux niveaux infranational et local afin de préserver la santé et le bien-être des personnes de tous âges.

Apéndice. Lograr una mejor inmunidad: El enfoque del curso de vida para una longevidad saludable

Esta publicación es un apéndice del documento técnico "Lograr una mejor inmunidad: el enfoque de curso de vida para una longevidad saludable", con las contribuciones de varios expertos en la materia dentro y fuera de la Organización Panamericana de la Salud (OPS). Este apéndice proporciona ejemplos de actividades dentro del programa nacional de inmunización que pueden mejorar las tasas de cobertura y reducir las oportunidades perdidas para cuatro grupos de población: mujeres embarazadas, adolescentes, trabajadores sanitarios y adultos mayores. Estos ejemplos traducen los principios y conceptos del Enfoque del Ciclo Vital en actividades concretas, que pueden ser utilizadas por los gestores de los programas nacionales de inmunización y por los vacunadores, respectivamente, para reforzar las tasas de cobertura de vacunación. Estos cuatro grupos representan etapas de la vida para las que existen vacunas muy eficaces y que pueden influir enormemente en sus capacidades sanitarias. La aplicación de dosis de vacunas de la serie primaria, de refuerzo y de recuperación en estos grupos es fundamental para cerrar las brechas de inmunidad emergentes. Las actividades se agrupan en ocho componentes (i) administración y promoción, (ii) equidad, (iii) recursos humanos y financiación, (iv) organización y prestación de servicios, (v) generación de demanda y participación de la comunidad, (vi) sistemas de información, (vii) formación y (viii) evaluación e investigación. Los ejemplos deben ser evaluados, adaptados, implementados y posiblemente ampliados por los Estados Miembros para alinearlos con los contextos nacionales y locales. Este documento forma parte de los esfuerzos de la OPS para promover la aplicación de un enfoque de inmunización a lo largo de la vida por parte de los países y territorios de las Américas y para apoyar a los Ministerios de Salud a establecer estrategias de salud pública a nivel subnacional y local para salvaguardar la salud y el bienestar de las personas de todas las edades.

The impact of the Mediterranean diet on immune function in older adults.

Diet is one of the lifestyle factors that is most amenable to intervention, and has a substantial effect on the potential for successful aging and mitigation of the risk of disease. Good nutrition is a pillar of healthy aging, and a large body of evidence attests to the benefits of the Mediterranean diet on the quality of the aging process. The Mediterranean diet comprises a wide range of nutrients which, both individually and collectively, exert positive effects on immunity, in large part mediated by the gut microbiota. In this article, we review the effect of the Mediterranean diet on immunity, and how its beneficial effects are mediated by the gut microbiota. We review the effects of certain key components of the Mediterranean dietary pattern, including vitamins, zinc, selenium, and polyphenols. Overall, the existing body of evidence convincingly demonstrates that the Mediterreanean diet affects immune health by maintaining a healthy body weight and reducing the risk of metabolic and cardiovascular diseases; by reducing inflammation and by promoting a healthy gut microbiota profile.

AIOLOS-Associated Inborn Errors of Immunity.

AIOLOS, encoded by the IKZF3 gene, belongs to the Ikaros zinc finger transcription factor family and plays a pivotal role in regulating lymphocyte development. Recently, heterozygous missense loss-of-function variants within the DNA-binding domain of the IKZF3 gene (G159R, N160S, and G191R) have been identified in patients with inborn errors of immunity (IEI). Additionally, a missense and a truncating variant (E82K and Q402X) leading to the AIOLOS haploinsufficiency have been documented. The majority of individuals with AIOLOS-associated IEI manifest recurrent sinopulmonary infections, as well as various bacterial and viral infections. The patients carrying the AIOLOSN160S variant exhibit severe immunodeficient phenotypes. In contrast, patients harboring AIOLOS haploinsufficient variants predominantly present with clinical phenotypes associated with immune dysregulation. A varying degree of B-lymphopenia and hypoimmunoglobulinemia was noted in approximately half of the patients. Mouse models of AIOLOSG159R and AIOLOSN160S variants (AiolosG158R and AiolosN159S in mice, respectively) recapitulated most of the immune abnormalities observed in the patients. Among these models, AiolosG158R mice prominently exhibited defects in early B cell differentiation resulting from mutant Aiolos interfering with Ikaros function through heterodimer formation. In contrast, AiolosN159S mice did not manifest early B cell differentiation defects. However, they displayed a distinct immune abnormality characterized by impaired induction of CD62L expression in lymphocytes, which is likely attributable to dysfunction of Ikaros, leading to defective lymphocyte homing to lymph nodes. Considering the diverse clinical phenotypes observed in the reported cases and the distinct molecular pathogenesis associated with each variant, further studies with more patients with AIOLOS-associated IEI would contribute to a better understanding of the clinical spectrum and underlying molecular mechanisms associated with this disorder.

Modulation of host immunity by sensory neurons.

Recent studies have uncovered a new role for sensory neurons in influencing mammalian host immunity, challenging conventional notions of the nervous and immune systems as separate entities. In this review we delve into this groundbreaking paradigm of neuroimmunology and discuss recent scientific evidence for the impact of sensory neurons on host responses against a wide range of pathogens and diseases, encompassing microbial infections and cancers. These valuable insights enhance our understanding of the interactions between the nervous and immune systems, and also pave the way for developing candidate innovative therapeutic interventions in immune-mediated diseases highlighting the importance of this interdisciplinary research field.

BIBR1532 combined with radiotherapy induces ferroptosis in NSCLC cells and activates cGAS-STING pathway to promote anti-tumor immunity.

BACKGROUND: Telomerase, by safeguarding damaged telomeres and bolstering DNA damage repair, has the capacity to heighten the radioresistance of tumour cells. Thus, in turn, can compromise the efficacy of radiotherapy (RT) and radioimmunotherapy. Our previous studies have revealed that the highly selective telomerase inhibitor, BIBR1532, possesses the potential to enhance the radiosensitivity of Non-small cell lung cancer (NSCLC). In this study, we delve further into the impact of BIBR1532 on the immune activation induced by RT and elucidate the underlying mechanisms. METHODS: Biological information analyses, immunofluorescence assays, western blot assays, flow cytometry analysis were conducted to elucidate the functions of the combination of BIBR1532 with radiotherapy in NSCLC. Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Both in vitro and in vivo studies were conducted to examine the antitumor effects. RESULTS: Our findings indicate that the confluence of BIBR1532 with RT significantly augments the activation of the cGAS-STING pathway in both in vivo and in vitro settings, thereby fostering an effective anti-tumoral immune response. The effects can be ascribed to two key processes. Firstly, ionizing radiation, in precipitating DNA double-strand breaks (DSBs), prompts the release of tumour-derived double-stranded DNA (dsDNA) into the cytoplasm. Subsequently, BIBR1532 amplifies the activation of antigen-presenting cells by dsDNA post-RT and instigates the cGAS-STING pathway. Secondly, BIBR1532 enhances the ferroptosis response in NSCLC following RT, thereby promoting unrestrained lipid peroxidation and elevated levels of reactive oxygen species (ROS) within tumour cells. This ultimately leads to mitochondrial stress and the release of endogenous mitochondrial DNA (mtDNA) into the cytoplasm, thus facilitating the activation of the STING pathway and the induction of a type I interferon (IFN)-linked adaptive immune response. CONCLUSION: This study underscores the potential of BIBR1532 as an efficacious and safe radiosensitizer and radioimmunotherapy synergist, providing robust preclinical research evidence for the treatment of NSCLC.

Effects of Antiretroviral Treatment on Central and Peripheral Immune Response in Mice with EcoHIV Infection.

HIV infection is an ongoing global health issue, despite increased access to antiretroviral therapy (ART). People living with HIV (PLWH) who are virally suppressed through ART still experience negative health outcomes, including neurocognitive impairment. It is increasingly evident that ART may act independently or in combination with HIV infection to alter the immune state, though this is difficult to disentangle in the clinical population. Thus, these experiments used multiplexed chemokine/cytokine arrays to assess peripheral (plasma) and brain (nucleus accumbens; NAc) expression of immune targets in the presence and absence of ART treatment in the EcoHIV mouse model. The findings identify the effects of EcoHIV infection and of treatment with bictegravir (B), emtricitabine (F), and tenofovir alafenamide (TAF) on the expression of numerous immune targets. In the NAc, this included EcoHIV-induced increases in IL-1α and IL-13 expression and B/F/TAF-induced reductions in KC/CXCL1. In the periphery, EcoHIV suppressed IL-6 and LIF expression, while B/F/TAF reduced IL-12p40 expression. In the absence of ART, IBA-1 expression was negatively correlated with CX3CL1 expression in the NAc of EcoHIV-infected mice. These findings identify distinct effects of ART and EcoHIV infection on peripheral and central immune factors and emphasize the need to consider ART effects on neural and immune outcomes.

Ironing out the role of ferroptosis in immunity.

Ferroptosis is a type of regulated cell death that drives the pathophysiology of many diseases. Oxidative stress is detectable in many types of regulated cell death, but only ferroptosis involves lipid peroxidation and iron dependency. Ferroptosis originates and propagates from several organelles, including the mitochondria, endoplasmic reticulum, Golgi, and lysosomes. Recent data have revealed that immune cells can both induce and undergo ferroptosis. A mechanistic understanding of how ferroptosis regulates immunity is critical to understanding how ferroptosis controls immune responses and how this is dysregulated in disease. Translationally, more work is needed to produce ferroptosis-modulating immunotherapeutics. This review focuses on the role of ferroptosis in immune-related diseases, including infection, autoimmune diseases, and cancer. We discuss how ferroptosis is regulated in immunity, how this regulation contributes to disease pathogenesis, and how targeting ferroptosis may lead to novel therapies.

Sialic acid-based probiotic intervention in lactating mothers improves the neonatal gut microbiota and immune responses by regulating sialylated milk oligosaccharide synthesis via the gut-breast axis.

Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.

Unveiling the gastric microbiota: implications for gastric carcinogenesis, immune responses, and clinical prospects.

High-throughput sequencing has ushered in a paradigm shift in gastric microbiota, breaking the stereotype that the stomach is hostile to microorganisms beyond H. pylori. Recent attention directed toward the composition and functionality of this 'community' has shed light on its potential relevance in cancer. The microbial composition in the stomach of health displays host specificity which changes throughout a person's lifespan and is subject to both external and internal factors. Distinctive alterations in gastric microbiome signature are discernible at different stages of gastric precancerous lesions and malignancy. The robust microbes that dominate in gastric malignant tissue are intricately implicated in gastric cancer susceptibility, carcinogenesis, and the modulation of immunosurveillance and immune escape. These revelations offer fresh avenues for utilizing gastric microbiota as predictive biomarkers in clinical settings. Furthermore, inter-individual microbiota variations partially account for differential responses to cancer immunotherapy. In this review, we summarize current literature on the influence of the gastric microbiota on gastric carcinogenesis, anti-tumor immunity and immunotherapy, providing insights into potential clinical applications.

Immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination among nursing home residents-Georgia, October 2020-July 2022.

BACKGROUND: Understanding the immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination is important in nursing home (NH) residents, a high-risk population. METHODS: An observational longitudinal evaluation of 37 consenting vaccinated NH residents with/without SARS-CoV-2 infection from October 2020 to July 2022 was conducted to characterize the immune response to spike protein due to infection and/or mRNA COVID-19 vaccine. Antibodies (IgG) to SARS-CoV-2 full-length spike, nucleocapsid, and receptor binding domain protein antigens were measured, and surrogate virus neutralization capacity was assessed using Meso Scale Discovery immunoassays. The participant's spike exposure status varied depending on the acquisition of infection or receipt of a vaccine dose. Longitudinal linear mixed effects modeling was used to describe trajectories based on the participant's last infection or vaccination; the primary series mRNA COVID-19 vaccine was considered two spike exposures. Mean antibody titer values from participants who developed an infection post receipt of mRNA COVID-19 vaccine were compared with those who did not. In a subset of participants (n = 15), memory B cell (MBC) S-specific IgG (%S IgG) responses were assessed using an ELISPOT assay. RESULTS: The median age of the 37 participants at enrollment was 70.5 years; 30 (81%) had prior SARS-CoV-2 infection, and 76% received Pfizer-BioNTech and 24% Moderna homologous vaccines. After an observed augmented effect with each spike exposure, a decline in the immune response, including %S IgG MBCs, was observed over time; the percent decline decreased with increasing spike exposures. Participants who developed an infection at least two weeks post-receipt of a vaccine were observed to have lower humoral antibody levels than those who did not develop an infection post-receipt. CONCLUSIONS: These findings suggest that understanding the durability of immune responses in this vulnerable NH population can help inform public health policy regarding the timing of booster vaccinations as new variants display immune escape.