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Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18-50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4ß7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis.
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PURPOSE: Identify variables, including moderating variables, associated with adolescents, young adults, and parents' intention to receive a COVID-19 vaccine in January 2021. DESIGN: Cross-sectional survey. SETTING: United States Midwestern academic medical center. SAMPLE: Adolescents (n = 242); young adults (n = 333); parents (n = 563). MEASURES: Associations between predictors-participant characteristics, general vaccine hesitancy, COVID-19 and vaccine knowledge, perceptions, and normative beliefs-and intention to receive a COVID-19 vaccine (outcome) were assessed. To determine variables impacting the strength of the relationship between predictors and outcome, moderators included 2020/2021 influenza vaccine receipt, having experienced discrimination, and primary sources of information for COVID-19. ANALYSIS: Multivariable logistic regression examined associations, including moderating effects, for adolescents, young adults, parents, and parents for child. RESULTS: With 20,231 email addresses receiving the survey, 1138 participants were included in the analysis. Intention to receive a COVID-19 vaccine was reported by 60.7% adolescents (n = 147), 65.2% young adults (n = 217), and 38.5% parents (n = 217) and 38.2% parents (n = 215) intended to vaccinate their child. Intention was associated with lower general vaccine hesitancy for adolescents (AOR = 1.50), young adults (AOR = 1.39), parents (AOR = 1.18), and parents' intention for their child (AOR = 1.17). Parents citing reputable medical experts as primary source of COVID-19 information positively moderated vaccine perceptions and intention for self (AOR = 8.25) and child (AOR = 6.37). CONCLUSION: Clinician training to address vaccine hesitancy may be effective at promoting positive COVID-19 vaccine perceptions.
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Vacinas contra COVID-19 , COVID-19 , Conhecimentos, Atitudes e Prática em Saúde , Intenção , Pais , Hesitação Vacinal , Humanos , Adolescente , Vacinas contra COVID-19/administração & dosagem , Estudos Transversais , Pais/psicologia , Masculino , Feminino , Adulto Jovem , COVID-19/prevenção & controle , COVID-19/psicologia , Adulto , Hesitação Vacinal/psicologia , Hesitação Vacinal/estatística & dados numéricos , SARS-CoV-2 , Etnicidade/estatística & dados numéricos , Etnicidade/psicologia , Inquéritos e QuestionáriosRESUMO
B memory (BM) cell responses were evaluated using peripheral blood mononuclear cells that were collected and cryopreserved during a Phase 1 trial of two live Shigella sonnei vaccine candidates WRSs2 and WRSs3. An ELISpot assay was used to measure IgG+ and IgA+ BM cell responses against S. sonnei LPS, IVP and IpaB antigens. Analysis of BM cell responses at baseline, and on days 28 and 56 post vaccination indicate that after a single oral dose of WRSs2 and WRSs3, both groups of vaccinees induced IgG+ and IgA+ BM cell responses that were variable in magnitude among subjects and reached significance to IVP and IpaB at several doses. The responses generally peaked at d28 after vaccination. The baseline as well as post-vaccination levels of IgA+ BM cells were relatively higher than IgG+ BM cells, but the maximum fold-increase at d28/d56 over baseline was greater for IgG+ than IgA+ BM cell responses. Furthermore, at the three highest vaccine doses, >60-90% of subjects were considered responders indicating a ≥2-fold higher IgG+ BM cell responses to IVP and IpaB post vaccination, while fewer subjects indicated the same level of response to LPS.
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Vacinas contra Shigella , Shigella sonnei , Humanos , Anticorpos Antibacterianos , Antígenos , Proteínas de Bactérias , Imunoglobulina A , Imunoglobulina G , Leucócitos Mononucleares , Lipopolissacarídeos , Vacinação , Vacinas Atenuadas , Ensaios Clínicos Fase I como AssuntoRESUMO
BACKGROUND: Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated. METHODS: Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or ANDV DNA vaccine delivered via needle-free jet injection. Cohorts 1 and 2 received 2 mg of DNA or placebo in a 3-dose (days 1, 29, 169) or 4-dose (days 1, 29, 57, 169) schedule, respectively. Cohorts 3 and 4 received 4 mg of DNA or placebo in the 3-dose and 4-dose schedule, respectively. Subjects were monitored for safety and neutralizing antibodies by pseudovirion neutralization assay (PsVNA50) and plaque reduction neutralization test (PRNT50). RESULTS: While 98% and 65% of subjects had at least 1 local or systemic solicited adverse event (AE), respectively, most AEs were mild or moderate; no related serious AEs were detected. Cohorts 2, 3, and 4 had higher seroconversion rates than cohort 1 and seropositivity of at least 80% by day 197, sustained through day 337. PsVNA50 geometric mean titers were highest for cohort 4 on and after day 197. CONCLUSIONS: This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response. Clinical Trials Registration. NCT03682107.
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Síndrome Pulmonar por Hantavirus , Orthohantavírus , Vacinas de DNA , Adulto , Humanos , Vacinas de DNA/efeitos adversos , Anticorpos Neutralizantes , DNA , Imunogenicidade da Vacina , Método Duplo-Cego , Anticorpos AntiviraisRESUMO
Shigella causes bacillary dysentery and is responsible for a high burden of disease globally. Several studies have emphasized the value of functional antibody activity to understand Shigella immunity and correlates of protection. The anti-microbial function of local (mucosal) antibodies and their contribution to preventing Shigella infection remain unknown. The goal of this study was to identify the functional humoral immune effectors elicited by two Shigella sonnei live oral vaccine candidates, WRSs2 and WRSs3. Complement-dependent bactericidal [serum bactericidal antibody (SBA)/bactericidal antibody (BA)] and opsonophagocytic killing antibody (OPKA) activity were determined in sera and stool extracts as indicators of systemic and local anti-microbial immunity. High levels of SBA/BA and OPKA were detected in serum as well as in fecal extracts from volunteers who received a single dose of WRSs2 and WRSs3. Functional antibody activity peaked on days 10 and 14 post-vaccination in fecal and serum samples, respectively. Bactericidal and OPKA titers were closely associated. Peak fold rises in functional antibody titers in serum and fecal extracts were also associated. Antibody activity interrogated in IgG and IgA purified from stool fractions identified IgG as the primary driver of mucosal bactericidal and OPKA activity, with minimal functional activity of IgA alone, highlighting an underappreciated role for IgG in bacterial clearance in the mucosa. The combination of IgG and IgA in equal proportions enhanced bactericidal and OPKA titers hinting at a co-operative or synergistic action. Our findings provide insight into the functional anti-microbial capacity of vaccine-induced mucosal IgG and IgA and propose an operative local humoral effector of protective immunity.IMPORTANCEThere is an urgent need for a safe, effective, and affordable vaccine against Shigella. Understanding the immunological underpinning of Shigella infection and the make-up of protective immunity is critical to achieve the best approach to prevent illness caused by this mucosal pathogen. We measured the complement-dependent bactericidal and opsonophagocytic antibody killing in serum and stool extracts from adult volunteers vaccinated with Shigella sonnei live oral vaccine candidates WRSs2 and WRSs3. For the first time, we detected functional antibody responses in stool samples that were correlated with those in sera. Using purified stool IgA and IgG fractions, we found that functional activity was mediated by IgG, with some help from IgA. These findings provide insight into the functional anti-microbial capacity of vaccine-induced mucosal IgG and IgA and support future studies to identify potential markers of protective mucosal immunity.
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Disenteria Bacilar , Shigella , Vacinas , Adulto , Humanos , Shigella sonnei , Disenteria Bacilar/prevenção & controle , Anticorpos Antibacterianos , Imunização , Vacinação , Mucosa , Imunoglobulina G , Imunoglobulina ARESUMO
BACKGROUND: Group A streptococci (GAS) are a major cause of pharyngitis in children. Recently, there were severe GAS outbreaks. The aims of this study were to assess pharyngeal colonization prevalence in healthy children, to assess different diagnostic definitions for GAS pharyngitis and to estimate incidence rates for these infections. METHODS: A 2-year longitudinal study was conducted in healthy children in the United States. Pharyngeal swabs were cultured every 3 months for GAS colonization. Serum antistreptolysin O, antideoxyribonuclease B (DNaseB) and antistreptococcal C5a peptidase (SCP) antibody titers were assessed at baseline. When participants developed a sore throat, pharyngeal swabs were collected for rapid antigen detection test (RADT) and culture, and antibody titers were determined in serum samples. A range of case definitions were used for GAS pharyngitis. RESULTS: A total of 422 children 3-12 years old were enrolled (140, 141 and 141 were 3-5, 6-9 and 10-12 years of age, respectively). The overall prevalence of GAS colonization during the study was 48%. Baseline antistreptolysin O, anti-DNaseB and anti-SCP antibody titers were higher for children older than 5 years. The incidence of GAS pharyngitis per 100 person-years was 15.9 for RADT/culture-proven and 4.6 for serologically confirmed pharyngitis. CONCLUSIONS: GAS throat colonization and pharyngitis were frequent in children 3-12 years old. The case definition employed impacted the measured incidence of GAS pharyngitis, with higher rates detected using RADT/culture-based definitions. These data suggest that case definition is important and that young children are exposed to GAS, which may inform plans for vaccine development and implementation.
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Faringite , Infecções Estreptocócicas , Criança , Humanos , Pré-Escolar , Estudos Longitudinais , Antiestreptolisina , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/diagnóstico , Sensibilidade e Especificidade , Streptococcus pyogenes , Faringite/epidemiologia , Faringite/diagnósticoRESUMO
As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209.
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Racially minoritized groups are more likely to experience COVID-19 vaccine hesitancy and have lower vaccination rates. As part of a multi-phase community-engaged project, we developed a train-the-trainer program in response to a needs assessment. "Community vaccine ambassadors" were trained to address COVID-19 vaccine hesitancy. We evaluated the program's feasibility, acceptability, and impact on participant confidence for COVID-19 vaccination conversations. Of the 33 ambassadors trained, 78.8% completed the initial evaluation; nearly all reported gaining knowledge (96.8%) and reported a high confidence with discussing COVID-19 vaccines (93.5%). At two-week follow-up, all respondents reported having a COVID-19 vaccination conversation with someone in their social network, reaching an estimated 134 people. A program that trains community vaccine ambassadors to deliver accurate information about COVID-19 vaccines may be an effective strategy for addressing vaccine hesitancy in racially minoritized communities.
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Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Comunicação , Conhecimento , Avaliação das Necessidades , VacinaçãoRESUMO
We describe the clinical characteristics and outcomes of 16 children and young adults with severe acute COVID-19 who were treated with tocilizumab. Patients who were discharged by day 28 were more likely to be treated with tocilizumab earlier in their COVID-19 illness and had lower ferritin and interleukin-6 levels compared with those who were not discharged by day 28.
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COVID-19 , Humanos , Criança , Adulto Jovem , SARS-CoV-2 , Resultado do Tratamento , Índice de Gravidade de Doença , Tratamento Farmacológico da COVID-19 , Hospitais , Estudos RetrospectivosRESUMO
BACKGROUND: Influenza A/H5N8 viruses infect poultry and wild birds in many countries. In 2021, the first human A/H5N8 cases were reported. METHODS: We conducted a phase I, cohort-randomized, double-blind, controlled trial of inactivated influenza A/H5N8 vaccine (clade 2.3.4.4c) administered with or without adjuvant. Cohort 1 subjects received either two doses of AS03-adjuvanted vaccine containing 3.75 µg or 15 µg hemagglutinin (HA); two doses of 15 µg HA unadjuvanted vaccine; or one dose of AS03-adjuvanted vaccine (3.75 µg or 15 µg HA), followed by one dose of non-adjuvanted vaccine (same HA content). Cohort 2 subjects received two doses of MF59-adjuvanted vaccine containing 3.75 µg or 15 µg HA, or 15 µg HA of non-adjuvanted vaccine. Subjects were followed for 13 months for safety and immunogenicity. RESULTS: We enrolled 386 adult subjects in good health. Solicited adverse events were generally mild and more common among subjects who received adjuvanted vaccines. Antibody responses (hemagglutination inhibition or microneutralization assays) were highest in the two-dose AS03 group, followed by the one-dose AS03 group, the MF59 groups, and the non-adjuvanted groups. Antibody levels returned to baseline 12 months after the second vaccination in all groups except the 15 µg AS03-adjuvanted group. Cross-reactive antibodies to clade 2.3.4.4b strains isolated from recent human cases were demonstrated in a subset of both 15 µg adjuvanted groups. CONCLUSIONS: Two doses of influenza A/H5N8 vaccine were well-tolerated. Immunogenicity improved with receipt of two doses of adjuvanted vaccine and higher antigen content. (Funded by the National Institute of Allergy and Infectious Diseases.
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BACKGROUND: We evaluated the associations between baseline influenza virus-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection in a controlled human infection study. METHODS: We inoculated unvaccinated healthy adults aged 18-49 years with an influenza A/California/04/2009/H1N1pdm-like virus (NCT04044352). We collected serial safety labs, serum for HAI and MN, and nasopharyngeal swabs for reverse-transcription polymerase chain reaction (RT-PCR) testing. Analyses used the putative seroprotective titer of ≥40 for HAI and MN. The primary clinical outcome was mild-to-moderate influenza disease (MMID), defined as ≥1 postchallenge positive qualitative RT-PCR test with a qualifying symptom/clinical finding. RESULTS: Of 76 participants given influenza virus challenge, 54 (71.1%) experienced MMID. Clinical illness was generally very mild. MMID attack rates among participants with baseline titers ≥40 by HAI and MN were 64.9% and 67.9%, respectively, while MMID attack rates among participants with baseline titers <40 by HAI and MN were 76.9% and 78.3%, respectively. The estimated odds of developing MMID decreased by 19% (odds ratio, 0.81 [95% confidence interval, .62-1.06]; P = .126) for every 2-fold increase in baseline HAI. There were no significant adverse events. CONCLUSIONS: We achieved a 71.1% attack rate of MMID. High baseline HAI and MN were associated with protection from illness. Clinical Trials Registration. NCT04044352.
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Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Humanos , Adulto , Influenza Humana/prevenção & controle , Anticorpos Antivirais , Projetos de Pesquisa , Testes de Inibição da HemaglutinaçãoRESUMO
The COVID-19 pandemic has left an indelible mark on global health, affecting individuals of all ages across diverse communities. While the virus has predominantly been associated with severe outcomes in adults, its impact on children has garnered increasing attention. Today, three COVID-19 vaccines are available for use in the U.S. and recommended by the Advisory Committee on Immunization Practices (ACIP). As of September 2023, ongoing genomic surveillance identified SARS-CoV-2 XBB sublineages as the most common circulating SARS-CoV-2 variants, constituting over 99% of sequenced SARS-CoV-2 specimens in the US. Recently, recommendations for COVID-19 vaccination were updated accordingly to the 2023-2024 Omicron-XBB.1.5-adapted monovalent COVID-19 vaccine to provide heightened protection against currently circulating SARS-CoV-2 XBB-sublineage variants. COVID-19 vaccines have proven to be safe, efficacious, and effective at protecting against COVID-19 and preventing severe illness in children and adolescents.
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BACKGROUND: Effective therapeutic agents for the treatment of COVID-19 have been investigated since the onset of the pandemic. Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been developed for the treatment of mild or moderate COVID disease in high-risk populations. Despite widespread use in the adult population, data are limited on the safety and efficacy of monoclonal antibody infusions in the adolescent and young adult population. METHODS: Patients who received bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for treatment of mild-to-moderate COVID-19 disease at Cincinnati Children's Hospital Medical Center from 5/1/2020 to 3/1/2022 were identified retrospectively. Patient data including demographics, adverse events, and outcomes were extracted from patients' charts and summarized by standard descriptive summaries. RESULTS: Ninety-four patients received monoclonal antibody therapy, of which 14 (14.9%) received either bamlanivimab or bamlanivimab-etesevimab, 54 (57.4%) received casirivimab-imdevimab, and 26 (27.6%) received sotrovimab. Ten patients (10.6%) experienced one or more infusion-related adverse event. Of the patients who experienced adverse events, all resolved with cessation of infusion. No life-threatening events or deaths occurred. Within 90 days of receiving a monoclonal antibody, 12 patients (12.7%) required additional medical care for ongoing COVID symptoms. Five of these were either hospitalized or received escalation of care while already in the hospital. All subsequently fully recovered. Neither infusion-related adverse events nor progression to hospitalization for ongoing COVID-19 symptoms following monoclonal antibody administration were associated with any particular underlying condition. CONCLUSIONS: Overall, monoclonal antibodies are reasonably well-tolerated COVID-19 therapies in high-risk adolescent and young adult populations.
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Tratamento Farmacológico da COVID-19 , Adolescente , Humanos , Adulto Jovem , Criança , SARS-CoV-2 , Estudos Retrospectivos , Anticorpos Monoclonais/efeitos adversos , Anticorpos NeutralizantesRESUMO
BackgroundWe report updated safety, efficacy, and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) from an ongoing phase 3 trial.MethodsAdults at increased risk of SARS-CoV-2 infection were randomized (2:1), stratified by age, to receive 2 doses of AZD1222 or placebo. The primary efficacy end point was confirmed SARS-CoV-2 reverse-transcriptase PCR-positive (RT-PCR-positive) symptomatic COVID-19 at 15 or more days after a second dose in baseline SARS-CoV-2-seronegative participants. The 21,634 and 10,816 participants were randomized to AZD1222 and placebo, respectively.FindingsData cutoff for this analysis was July 30, 2021; median follow-up from second dose was 78 and 71 days for the double-blind period (censoring at unblinding or nonstudy COVID-19 vaccination) and 201 and 82 days for the period to nonstudy COVID-19 vaccination (regardless of unblinding) in the AZD1222 and placebo groups, respectively. For the primary efficacy end point in the double-blind period (141 and 184 events; incidence rates: 39.2 and 118.8 per 1,000 person years), vaccine efficacy was 67.0% (P < 0.001). In the period to nonstudy COVID-19 vaccination, incidence of events remained consistently low and stable through 6 months in the AZD1222 group; for the primary efficacy end point (328 and 219 events; incidence rates: 36.4, 108.4) and severe/critical disease (5 and 13 events; incidence rates: 0.6, 6.4), respective vaccine efficacy estimates were 65.1% and 92.1%. AZD1222 elicited humoral immune responses over time, with waning at day 180. No emergent safety issues were seen.ConclusionAZD1222 is safe and well tolerated, demonstrating durable protection and immunogenicity with median follow-up (AZD1222 group) of 6 months.Trial registrationClinicalTrials.gov NCT04516746.FundingAstraZeneca; US government.
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Vacinas contra COVID-19 , COVID-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Humanos , SARS-CoV-2 , VacinaçãoRESUMO
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.
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COVID-19 , Vacinas Virais , Ad26COVS1 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Humanos , RNA Mensageiro , SARS-CoV-2/genética , Vacinas Sintéticas , Vacinas de mRNARESUMO
Shigella-controlled human infection models (CHIMs) are an invaluable tool utilized by the vaccine community to combat one of the leading global causes of infectious diarrhea, which affects infants, children and adults regardless of socioeconomic status. The impact of shigellosis disproportionately affects children in low- and middle-income countries (LMICs) resulting in cognitive and physical stunting, perpetuating a cycle that must be halted. Shigella-CHIMs not only facilitate the early evaluation of enteric countermeasures and up-selection of the most promising products but also provide insight into mechanisms of infection and immunity that are not possible utilizing animal models or in vitro systems. The greater understanding of shigellosis obtained in CHIMs builds and empowers the development of new generation solutions to global health issues which are unattainable in the conventional laboratory and clinical settings. Therefore, refining, mining and expansion of safe and reproducible infection models hold the potential to create effective means to end diarrheal disease and associated co-morbidities associated with Shigella infection.
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BACKGROUND: Pregnant women were excluded from investigational trials of COVID-19 vaccines. Limited data are available to inform pregnant and postpartum women on their decisions to receive a COVID-19 vaccine. METHODS: The goal of this observational, prospective cohort study is to evaluate the immunogenicity and safety of various Emergency Use Authorization (EUA) or licensed COVID-19 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in mothers and infants. The study is adaptive, allowing additional groups to be added as new vaccines or vaccine regimens are authorized. Up to 20 clinical research institutions in the United States (U.S.) will be included. Approximately 200 pregnant women and 65 postpartum women will be enrolled per EUA or licensed COVID-19 vaccine formulation in the U.S. This study will include pregnant and postpartum women of all ages with and without chronic medical conditions. Their infants will be enrolled and followed beginning at birth in the pregnant cohort and beginning at the earliest possible time point in the postpartum cohort. Blood samples will be collected for immunogenicity outcomes and pregnancy and birth outcomes assessed among women and infants. Primary analyses will be descriptive and done by vaccine type and/or platform. DISCUSSION: Given the long-standing and legitimate challenges of enrolling pregnant individuals into clinical trials early in the vaccine development pipeline, this study protocol describes our current study and provides a template to inform the collection of data for pregnant individuals receiving COVID-19 or other vaccines. TRIAL REGISTRATION: NCT05031468 .
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Vacinas contra COVID-19 , COVID-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Lactação , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. METHODS: In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 µg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×1010 virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 µg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. RESULTS: Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. CONCLUSIONS: Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).
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Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Ad26COVS1/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacina BNT162/imunologia , Vacinas contra COVID-19/imunologia , Imunogenicidade da Vacina , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Imunização Secundária/efeitos adversos , Injeções Intramusculares/efeitos adversos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologiaRESUMO
BACKGROUND: Pneumococcal conjugate vaccines (PCVs) have significantly reduced pneumococcal disease, but disease from non-PCV serotypes remains. The safety, tolerability, and immunogenicity of a 20-valent PCV (PCV20) were evaluated. METHODS: This pivotal phase 3, randomized, double-blind study enrolled adults into 3 age groups (≥60, 50-59, and 18-49 years) at US and Swedish sites. Participants were randomized to receive 1 PCV20 or 13-valent PCV (PCV13) dose. After 1 month, participants aged ≥60 years also received 1 dose of saline or 23-valent polysaccharide vaccine (PPSV23). Safety assessments included local reactions, systemic events, adverse events, serious adverse events, and newly diagnosed chronic medical conditions. Opsonophagocytic activity geometric mean titers 1 month after PCV20 were compared with 13 matched serotypes after PCV13 and 7 additional serotypes after PPSV23 in participants aged ≥60 years; noninferiority was declared if the lower bound of the 2-sided 95% confidence interval for the opsonophagocytic activity geometric mean titer ratio (ratio of PCV20/saline to PCV13/PPSV23 group) was >0.5. PCV20-elicited immune responses in younger participants were also bridged to those in 60-64-year-olds. RESULTS: The severity and frequency of prompted local reactions and systemic events were similar after PCV20 or PCV13; no safety concerns were identified. Primary immunogenicity objectives were met, with immune responses after PCV20 noninferior to 13 matched serotypes after PCV13 and to 6 additional PPSV23 serotypes in participants aged ≥60 years; serotype 8 missed the statistical noninferiority criterion. PCV20 induced robust responses to all 20 vaccine serotypes across age groups. CONCLUSIONS: PCV20 was safe and well tolerated, with immunogenicity comparable to that of PCV13 or PPSV23. PCV20 is anticipated to expand protection against pneumococcal disease in adults. CLINICAL TRIALS REGISTRATION: NCT03760146.