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Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.
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Vacina contra Herpes Zoster/imunologia , Imunidade Adaptativa , Adulto , Idoso , Envelhecimento , Formação de Anticorpos , Linfócitos T CD4-Positivos/imunologia , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Fosfatos de Inositol/imunologia , Estudos Longitudinais , Masculino , Metabolômica , Pessoa de Meia-Idade , Caracteres Sexuais , Esteróis/metabolismo , Carga ViralRESUMO
BACKGROUND: Influenza A (H7N9) has caused multiple disease waves with evidence of strain diversification. Optimal influenza A (H7N9) prime-boost vaccine strategies are unknown. METHODS: We recruited participants who had received monovalent inactivated A/Shanghai/2/2013 (H7N9) vaccine (MIV) approximately 5 years earlier, as follows: MIV with MF59 (MF59 × 2 group), MIV with AS03 (AS03 × 2 group), unadjuvanted MIV (No Adj group), MIV with MF59 or AS03 followed by unadjuvanted MIV (Adjx1 group), and A/H7-naive (unprimed group). Participants were randomized to receive 1 dose of AS03-adjuvanted or unadjuvanted A/Hong Kong/125/2017 (H7N9) MIV and were followed for safety and immunogenicity using hemagglutination inhibition (HAI) and neutralizing antibody assays. RESULTS: We enrolled 304 participants: 153 received the adjuvanted boost and 151 received the unadjuvanted boost. At 21 days postvaccination, the proportion of participants with HAI antibody titers against the boosting vaccine strain of ≥40 in the adjuvanted and unadjuvanted arms, respectively, were 88% and 49% in MF59 × 2 group, 89% and 75% in AS03 × 2 group, 59% and 20% in No Adj group, 94% and 55% in Adjx1group, and 9% and 11% in unprimed group. CONCLUSIONS: Serologic responses to a heterologous A(H7N9) MIV boost were highest in participants primed and boosted with adjuvant-containing regimens. CLINICAL TRIALS REGISTRATION: NCT03738241.
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Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Humanos , Adjuvantes Imunológicos , Anticorpos Antivirais , China , Testes de Inibição da Hemaglutinação , Imunogenicidade da Vacina , Influenza Humana/prevenção & controle , Polissorbatos , EsqualenoRESUMO
INTRODUCTION: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. METHODS: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15â µg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed. RESULTS: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6-212.6) among participants who received homologous, adjuvanted 3.75â µg + AS03/2017 doses with delayed boost interval. CONCLUSIONS: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807.
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Anticorpos Antivirais , Imunização Secundária , Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Vacinas de Produtos Inativados , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Anticorpos Antivirais/sangue , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Adulto Jovem , Esquemas de Imunização , Testes de Inibição da Hemaglutinação , Estados Unidos , Imunogenicidade da Vacina , Anticorpos Neutralizantes/sangue , Polissorbatos/administração & dosagem , Polissorbatos/efeitos adversos , alfa-Tocoferol/administração & dosagem , alfa-Tocoferol/efeitos adversos , Esqualeno/administração & dosagem , Esqualeno/efeitos adversos , Esqualeno/imunologia , Voluntários Saudáveis , Combinação de Medicamentos , Adjuvantes de Vacinas/administração & dosagem , Vacinação/métodos , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversosRESUMO
BACKGROUND: Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions. METHODS: A post hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, coronavirus disease 2019 (COVID-19) vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS individuals starting at 14 days after completion of the primary series through the blinded phase for each of the 4 trials. An analysis of participants living with well-controlled human immunodeficiency virus was conducted using the same methods. RESULTS: A total of 3852/30 351 (12.7%) Moderna participants, 3088/29 868 (10.3%) Novavax participants, 3549/32 380 (11.0%) AstraZeneca participants, and 5047/43 788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (vs placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants versus non-TIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with human immunodeficiency virus. CONCLUSIONS: For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared with those with non-TIS in the 4 COVID-19 vaccine randomized controlled efficacy trials.
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Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Eficácia de Vacinas , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Masculino , Feminino , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Adulto , Hospedeiro Imunocomprometido , Idoso , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.
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Vacina de mRNA-1273 contra 2019-nCoV , Adulto , Humanos , Vacinas Combinadas , Protocolos Clínicos , RNA Mensageiro/genéticaRESUMO
The coronavirus disease 2019 (COVID-19) pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for infectious diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, female faculty, underrepresented in medicine and science faculty and particularly ESF, experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic.
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COVID-19 , Doenças Transmissíveis , Humanos , Feminino , Grupos Minoritários , Pandemias , Docentes de MedicinaRESUMO
In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.
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COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Anticorpos Neutralizantes , Vacinas Combinadas , Anticorpos AntiviraisRESUMO
PURPOSE OF REVIEW: The successes of the coronavirus disease 2019 (COVID-19) mRNA vaccines have accelerated the development of mRNA vaccines against other respiratory pathogens. The aim of this review is to highlight COVID-19 mRNA vaccine advances and provide an update on the progress of mRNA vaccine development against other respiratory pathogens. RECENT FINDINGS: The COVID-19 mRNA vaccines demonstrated effectiveness in preventing severe COVID-19 and death. H7N9 and H10N8 avian influenza mRNA vaccines have demonstrated safety and immunogenicity in phase 1 clinical trials. Numerous seasonal influenza mRNA vaccines are in phase 1-3 clinical trials. Respiratory syncytial virus (RSV) mRNA vaccines have progressed to phase 2-3 clinical trials in adults and a phase 1 clinical trial in children. A combined human metapneumovirus and parainfluenza-3 mRNA vaccines was found to be well tolerated and immunogenic in a phase 1 trial among adults and trials are being conducted among children. Clinical trials of mRNA vaccines combining antigens from multiple respiratory viruses are underway. SUMMARY: The development of mRNA vaccines against respiratory viruses has progressed rapidly in recent years. Promising vaccine candidates are moving through the clinical development pathway to test their efficacy in preventing disease against respiratory viral pathogens.
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COVID-19 , Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Influenza Aviária , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Adulto , Criança , Animais , Humanos , Vacinas contra COVID-19 , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/genética , Infecções por Vírus Respiratório Sincicial/prevenção & controleRESUMO
BACKGROUND: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. OBJECTIVE: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). DESIGN: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]). SETTING: 94 hospitals in 10 countries (86% U.S. participants). PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: SOC. MEASUREMENTS: 28-day mortality and recovery. RESULTS: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages. LIMITATION: Unmeasured confounding. CONCLUSION: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.
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Antivirais , Tratamento Farmacológico da COVID-19 , Adulto , Humanos , Antivirais/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Dexametasona , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B-cell disorders associated with an increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by 2 months. Responses assessed at 3 and 12 months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color Interferon-γ and Interleukin-2FLUOROSPOT assays were compared to historic controls matched by age and sex. About 62 patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, p = .03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs. 36%, respectively, p = .23). The CD4+ T-cell response to vaccination was significantly lower in study participants compared to controls (54% vs. 96%, p < .001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs. 73%, p = .008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n = 47), 24% had antibody titers below the response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T-cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed.
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Vacina contra Herpes Zoster/uso terapêutico , Herpes Zoster/prevenção & controle , Imunidade Celular , Imunidade Humoral , Leucemia Linfocítica Crônica de Células B/complicações , Linfocitose/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Feminino , Herpes Zoster/imunologia , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Linfocitose/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4+ and CD8+ T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8+CD57+ senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4+CD69+CD57+PD1+ and CD8+CD69+CD57+PD1+ T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8+ effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4+ and CD8+ proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ.
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Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Vacina contra Herpes Zoster/imunologia , Herpesvirus Humano 3/imunologia , Imunidade Celular , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Feminino , Vacina contra Herpes Zoster/administração & dosagem , Humanos , Memória Imunológica , Interferon gama/imunologia , Interleucina-2/imunologia , Proteína 1 de Membrana Associada ao Lisossomo/imunologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Vacinação , Adulto JovemRESUMO
The QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Germantown, MD) interferon gamma release assay (IGRA) received FDA clearance in 2017 and will replace the prior version of the assay, the QFT-Gold In-Tube (QFT-GIT). Here, we compared performances of the QFT-Plus assay and the QFT-GIT version in a diverse patient population, including patients undergoing evaluation for or follow-up of latent tuberculosis infection (LTBI; n = 39) or active TB infection (n = 3), and in health care workers (HCWs; n = 119) at Mayo Clinic (Rochester, MN). Compared to the QFT-GIT, the QFT-Plus assay showed 91.2% (31/34) positive, 98.4% (124/126) negative, and 96.6% (156/161) overall qualitative agreement among the 161 enrolled subjects, with a Cohen's kappa value of 0.91 (excellent interrater agreement). Among the 28 patients diagnosed with LTBI at the time of enrollment, the QFT-GIT and QFT-Plus assays agreed in 24 (85.7%) patients; in all four discordant patients, the positivity of the QFT-GIT or QFT-Plus IGRA was associated with low-level interferon gamma (IFN-γ) reactivity, ranging from 0.36 IU/ml to 0.66 IU/ml. Additionally, we document a high degree of correlation between IFN-γ levels in the QFT-GIT TB antigen tube and each of the two QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes (Pearson's correlation coefficients [R] > 0.95). Overall, we show comparable results between the QFT-GIT and QFT-Plus assays in our study population composed of subjects presenting with a diverse spectrum of TB infections. Our findings suggest that the necessary transition to the QFT-Plus assay will be associated with a minimal difference in assay performance characteristics.
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Emigrantes e Imigrantes/estatística & dados numéricos , Pessoal de Saúde/estatística & dados numéricos , Testes de Liberação de Interferon-gama/normas , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Humanos , Interferon gama/metabolismo , Tuberculose Latente/diagnóstico , Masculino , Pessoa de Meia-Idade , Minnesota , Mycobacterium tuberculosis/imunologia , Estudos Prospectivos , Adulto JovemRESUMO
Infection is the cause of death in 30% to 50% of patients with chronic lymphocytic leukemia (CLL). A major strategy to decrease infection risk is vaccination. However, vaccine response rates in patients with CLL are typically insufficient. Recent studies have demonstrated that individuals with clinical monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, also have an increased risk of infection and thus could benefit from vaccines. However, there are no data on vaccine responses in the MBL population. This article reviews the immunodeficiency of CLL and MBL, discusses the recommended vaccines and data on vaccine immunogenicity in patients with CLL, and outlines the need to develop more effective vaccine strategies in this population of patients at high risk for infection.
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Imunização , Controle de Infecções , Infecções/etiologia , Leucemia Linfocítica Crônica de Células B/complicações , Linfocitose/complicações , Linfocitose/patologia , Lesões Pré-Cancerosas , Humanos , Controle de Infecções/métodos , Leucemia Linfocítica Crônica de Células B/imunologia , Linfocitose/imunologia , Risco , Vacinação , Vacinas/imunologiaRESUMO
Background: Studies have demonstrated low hepatitis A virus (HAV) vaccination rates among persons with HIV (PWH). Methods: We conducted a retrospective study of persons entering HIV care at two clinics in Houston, Texas between 2010 and 2018. We defined those eligible for HAV vaccination as those who had no history of HAV vaccination and had a negative anti-HAV IgG at entry to care. Kaplan-Meier curves summarized time to receipt of HAV vaccines. The proportions of patients who received 1 and 2 HAV vaccines at 6, 12, and 24 months were estimated. Cox proportional hazards regression evaluated associations between patient characteristics and vaccination. Significant factors were included in a multivariable Cox proportional hazards model. Results: Of 6,515 patients, 1372 were eligible for HAV vaccination. Of eligible patients, 29.2 % received 1 HAV vaccination at 6 months, 37.1 % at 12 months, and 47.8 % at 24 months. At 6 months, 10 % received 2 HAV vaccinations, 21.1 % at 12 months, and 33.4 % at 24 months. In multivariable analysis, men who have sex with men (adjusted HR 1.35, 95 % CI 1.06, 1.73) or those who had CD4 count ≥ 200 cells/µl (adjusted HR 2.52, 95 % CI 1.89, 3.37) had their second vaccination sooner than those who were not men who have sex with men or who had CD4 counts < 200 cells/µl, respectively. Patients > 50 years of age had their second vaccination sooner than those aged 30-50 years (adjusted HR 1.47, 95 % CI 1.08, 1.99). Those with active substance history had a longer time to second vaccination compared to those with no substance use history (adjusted HR 0.57, 95 % CI 0.40, 0.82). Conclusions: HAV vaccination rates were low and highlight the need for effective solutions to address HAV immunization gaps in PWH, especially among young patients, those with active substance use disorders, and those with significant immunocompromise.
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Background: Research gaps exist on the use of medications for opioid use disorder (OUD) among birthing people. Methods: This retrospective cohort study included people who underwent childbirth deliveries during 2017-2020 and had a diagnosis of OUD identified from a national private insurance claims database. Buprenorphine prescriptions received during the year before childbirth and the year after childbirth were obtained from pharmacy claims. Logistic regressions were used to estimate associations between receipt of buprenorphine and individual and state-level factors. Results: Among a sample of 1,523 birthing people diagnosed with OUD, 540 (35.5 %) received buprenorphine during the pregnancy or postpartum periods. About half (51.5 %) of new recipients of buprenorphine received treatment for at least six months and, of those, one-third experienced a treatment interruption. The buprenorphine receipt rate differed significantly by race and ethnicity: 28.8 % of non-Hispanic Black birthing people with OUD and 22.8 % of Hispanic birthing people with OUD received buprenorphine treatment in contrast to 37.7 % of non-Hispanic white birthing people (aOR 0.53 [95 % CI 0.35-0.81] and 0.59 [95 % CI 0.37-0.96], respectively). The buprenorphine use rate increased over time from 29.7 % in 2017 to 42.9 % in 2020. Birthing people living in states with punitive policies related to substance use in pregnancy had the lowest buprenorphine use rate of 22.7 % as compared to 43.0 % in states with least restrictive policies. Conclusion: In this national sample of privately-insured individuals, by 2020, 42.9 % of birthing people with OUD received buprenorphine treatment. Treatment discontinuation and interruptions were common in the period surrounding childbirth.
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Background: Studies have demonstrated low hepatitis B virus (HBV) vaccine series completion among persons with human immunodeficiency virus (HIV). Methods: We conducted a retrospective record review of persons entering HIV care at 2 clinics in Houston, Texas, between 2010 and 2018. Kaplan-Meier curves summarized time to receipt of HBV vaccines for those eligible for vaccination. We estimated the proportions of patients who had received 1, 2, or 3 HBV vaccine doses at 12 and 24 months after entry to care. A Prentice Williams and Peterson total time model was used to evaluate associations between patient characteristics and time to vaccination. Results: Of the 5357 patients who entered care, 2718 were eligible for HBV vaccination. After 2 years of follow-up, 51.2% of those eligible had received 1 HBV vaccine, 43.2% had received 2, and 28.4% received 3 vaccines. With adjustment for significant cofactors, patients whose CD4 cell count was ≥200/µL (adjusted hazard ratio [aHR], 1.43 [95% confidence interval (CI), 1.29-1.59]) and transgender patients (1.49 [1.08-2.04]) received any given vaccine dose sooner than those with CD4 cell counts <200/µL or cisgender patients, respectively. Compared with non-Hispanic whites, Hispanic patients were vaccinated sooner (aHR, 1.28 [95% CI, 1.07-1.53]). Those with an active substance use history had a significantly longer time to vaccination than those with no substance use history (aHR, 0.73 [95% CI, .62-.85]). Conclusions: Strategies are needed to increase HBV vaccine completion rates in our study population, particularly among those with CD4 cell counts <200/µL or with a substance use disorder.
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Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.
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In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent SARS-CoV-2 mRNA vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wildtype spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.
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In this brief report, we compare the magnitude and durability of the serologic response of one versus two doses (separated by 56 days) of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults.
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Background: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. Methods: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. Results: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.