RESUMO
Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two subunit RSV vaccines (Arexvy [GSK] and Abrysvo [Pfizer]) received approval from the U.S. Food and Drug Administration (FDA). In June 2023, ACIP recommended that adults aged ≥60 years may receive a single dose of RSV vaccine, using shared clinical decision-making. In support of development of this policy, our objective was to assess the cost-effectiveness of RSV vaccination in the general population in this age group. We used a decision-analytical model of RSV over a two-year timeframe using data from published literature, FDA documents, epidemiological databases, and manufacturer data. We tracked RSV-associated outpatient, emergency department, inpatient healthcare utilization, RSV-attributable deaths, quality-adjusted life-years lost (QALYs), and societal costs. The societal cost per QALY saved from RSV vaccination depended on age group and product: adults aged ≥60 years, $196,842 for GSK's vaccine and $176,557 for Pfizer's vaccine; adults ≥65 years, $162,138 for GSK and $146,543 for Pfizer; adults 60- <65 years, $385,829 for GSK and $331,486 for Pfizer. Vaccine efficacy, incidence of RSV hospitalization, and vaccine cost had the greatest influence on cost per QALY. Cost per QALY saved decreased as the age of those vaccinated increased. Inputs such as long-term efficacy are uncertain. RSV vaccination in adults aged ≥60 years may be cost-effective, particularly in those of more advanced age. Lower vaccine acquisition costs and persistent efficacy beyond two RSV seasons would render RSV vaccination more cost-effective for a broader target population. PRIMARY FUNDING SOURCE: US Centers for Disease Control and Prevention.
Assuntos
Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vacinação , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/economia , Vacinas contra Vírus Sincicial Respiratório/economia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Idoso , Pessoa de Meia-Idade , Vacinação/economia , Vacinação/métodos , Vírus Sincicial Respiratório Humano/imunologia , Masculino , Idoso de 80 Anos ou mais , Feminino , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody (mAb) licensed for the prevention of respiratory syncytial virus (RSV)-associated lower respiratory tract disease in neonates, infants and medically vulnerable children. We characterized RSV isolates recovered from participants enrolled in MEDLEY: a randomized, palivizumab-controlled phase 2/3 trial of nirsevimab in infants born preterm and/or with congenital heart disease or chronic lung disease of prematurity. METHODS: Participants were assessed in two RSV seasons (Season 1 and 2). Season 1 participants were randomized (2:1) to receive a single dose of nirsevimab (50 mg if weight <5 kg or 100 mg if weight ≥5 kg in Season 1; 200 mg in Season 2) followed by four monthly doses of placebo, or five once-monthly doses of palivizumab (15 mg/kg weight per dose). Season 2 participants continued nirsevimab and placebo (nirsevimab/nirsevimab) or were re-randomized (1:1) to switch to nirsevimab (palivizumab/nirsevimab) or continue palivizumab (palivizumab/palivizumab). Cases of RSV infection were identified by central testing of nasal swabs from participants seeking medical attention for respiratory illnesses. Nirsevimab and palivizumab binding site substitutions were assessed via microneutralization assay. RESULTS: Twenty-five cases of confirmed RSV infection were observed during the trial and sequenced: 12 in nirsevimab recipients and 10 in palivizumab recipients during Season 1, and 1 case in each Season 2 group. Molecular sequencing of RSV A (n = 14) isolates detected no nirsevimab binding site substitutions, and 3 palivizumab neutralization-resistant substitutions (Lys272Met, Lys272Thr, Ser275Leu). The nirsevimab binding site Ile206Met:Gln209Arg and Ile206Met:Gln209Arg:Ser211Asn substitutions were the only anti-RSV mAb binding site substitutions detected among RSV B isolates (n = 11). Nirsevimab neutralized all nirsevimab and palivizumab binding site substitutions in RSV A and B isolates recovered from MEDLEY participants. CONCLUSION: No binding site substitution detected during MEDLEY affected RSV susceptibility to nirsevimab neutralization.
Assuntos
Anticorpos Monoclonais Humanizados , Antivirais , Palivizumab , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Palivizumab/uso terapêutico , Palivizumab/administração & dosagem , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Lactente , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Método Duplo-Cego , Masculino , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Vírus Sincicial Respiratório Humano/genética , Feminino , Recém-Nascido , Anticorpos Antivirais/imunologia , Pré-Escolar , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangueRESUMO
The search for safe and efficacious products to prevent severe respiratory syncytial virus (RSV) disease in young infants has lasted more than 60 years. In high-income and middle-income countries, two new products have been authorised: an RSV monoclonal antibody for administration to infants (nirsevimab) and an RSV prefusion F maternal vaccine (RSVpreF [Pfizer, Puurs, Belgium]) for administration to pregnant people. These products are not yet available in low-income and lower-middle-income countries, where most RSV deaths occur. Other papers in this Series describe the acute burden of RSV disease in young children, the effects of RSV infection in early childhood on long-term lung health, and the burden of RSV disease and disease prevention products in older adults. In this Series paper, we briefly review the efficacy, effectiveness, and safety of nirsevimab and RSVpreF maternal vaccine for protection of infants. We then explore potential regulatory, policy, and implementation pathways and provide case studies of intervention uptake in Spain and Argentina, and considerations for use in Kenya. We also explore the health economic evidence to inform product introduction decisions. With sufficient political will and affordable pricing, RSV disease prevention in infants can become a global reality.
Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/imunologia , Lactente , Feminino , Gravidez , Vírus Sincicial Respiratório Humano/imunologia , Vacinação , Pré-EscolarRESUMO
Respiratory syncytial virus (RSV) is the most common cause of hospitalization among U.S. infants. CDC recommends RSV vaccination for pregnant persons or administration of RSV antibody (nirsevimab) to infants aged <8 months to prevent RSV lower respiratory tract disease among infants. To determine maternal and infant RSV immunization coverage for the 2023-24 RSV season, CDC conducted an Internet panel survey during March 26-April 11, 2024. Among 678 women at 32-36 weeks' gestation during September 2023-January 2024, 32.6% reported receipt of an RSV vaccine any time during pregnancy. Among 866 women with an infant born during August 2023-March 2024, 44.6% reported receipt of nirsevimab by the infant. Overall, 55.8% of infants were protected by maternal RSV vaccine, nirsevimab, or both. Provider recommendation for maternal vaccination or infant nirsevimab was associated with higher immunization coverage, whereas lack of a provider recommendation was the main reason for not getting RSV immunization. The main reason for definitely or probably not getting nirsevimab for infants was concern about the long-term safety for the infant. Activities supporting providers to make RSV prevention recommendations and have informative conversations with patients might increase the proportion of infants protected against severe RSV disease. CDC and the American College of Obstetricians and Gynecologists have resources to assist providers in effectively communicating the importance of immunization.
Assuntos
Anticorpos Monoclonais Humanizados , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Humanos , Estados Unidos , Feminino , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Lactente , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vacinas contra Vírus Sincicial Respiratório/imunologia , Gravidez , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Anticorpos Antivirais/sangue , Vacinação/estatística & dados numéricos , Adulto Jovem , Recém-Nascido , Vírus Sincicial Respiratório Humano/imunologiaRESUMO
The respiratory syncytial virus (RSV) fusion (F) glycoprotein is highly immunogenic in its prefusion (pre-F) conformation. However, the protein is unstable, and its conformation must be stabilized for it to function effectively as an immunogen in vaccines. We present a mutagenesis strategy to arrest the RSV F protein in its pre-F state by blocking localized changes in protein structure that accompany large-scale conformational rearrangements. We generated a series of mutants and screened them in vitro to assess their potential for forming a stable pre-F. In animals, the immunogenicity of a representative mutant F protein, with a conformation confirmed by cryo-electron microscopy, elicited levels of neutralizing antibodies and protection against RSV-induced lung damage that were comparable to those of DS-Cav1, a pre-F used in a licensed vaccine.
Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Proteínas Virais de Fusão , Animais , Humanos , Camundongos , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Microscopia Crioeletrônica , Imunogenicidade da Vacina , Pulmão/virologia , Camundongos Endogâmicos BALB C , Mutagênese , Mutação , Conformação Proteica , Estabilidade Proteica , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/química , Vacinas contra Vírus Sincicial Respiratório/genética , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/imunologia , Proteínas Virais de Fusão/química , Proteínas Virais de Fusão/imunologia , Proteínas Virais de Fusão/genéticaAssuntos
Antivirais , Quinazolinas , Infecções por Vírus Respiratório Sincicial , Sulfonas , Tiazepinas , Pré-Escolar , Humanos , Lactente , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/imunologia , Sulfonas/administração & dosagem , Sulfonas/efeitos adversos , Tiazepinas/administração & dosagem , Tiazepinas/efeitos adversos , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
Recent studies have documented prolonged expression of viral antigens and RNA and associated inflammation after infection with SARS-CoV-2 in a substantial proportion of infected patients. The persisting SARS-CoV-2 effects and findings, with inflammation associated with continued detection of viral antigens, especially resemble those previously reported for influenza virus, as well as respiratory syncytial virus (RSV). The reports indicate the need for improved insight into the mechanisms whereby post-SARS-CoV-2 infection-related illness is apparently more common and perhaps even more persistent after infection than observed for other respiratory viruses.
Assuntos
Antígenos Virais , COVID-19 , Inflamação , Infecções por Vírus Respiratório Sincicial , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Antígenos Virais/imunologia , Inflamação/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Infecções por Vírus Respiratório Sincicial/imunologia , Orthomyxoviridae/imunologia , Orthomyxoviridae/genética , Influenza Humana/virologia , Influenza Humana/imunologia , Vírus Sinciciais Respiratórios/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/genéticaRESUMO
Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes respiratory illnesses, ranging from mild symptoms to severe lower respiratory tract infections in infants and older adults. This virus is responsible for one-third of pneumonia deaths in the pediatric population; however, there are currently only a few effective vaccines. A better understanding of the RSV-host relationship at the molecular level may lead to a more effective management of RSV-related symptoms. The fractalkine (CX3CL1) receptor (CX3CR1) is a co-receptor for RSV expressed by airway epithelial cells and diverse immune cells. RSV G protein binds to the CX3CR1 receptor via a highly conserved amino acid motif (CX3C motif), which is also present in CX3CL1. The CX3CL1-CX3CR1 axis is involved in the activation and infiltration of immune cells into the infected lung. The presence of the RSV G protein alters the natural functions of the CX3CR1-CX3CL1 axis and modifies the host's immune response, an aspects that need to be considered in the development of an efficient vaccine and specific pharmacological treatment.
Assuntos
Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1 , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Infecções por Vírus Respiratório Sincicial/metabolismo , Quimiocina CX3CL1/metabolismo , Receptor 1 de Quimiocina CX3C/metabolismo , Vírus Sincicial Respiratório Humano/imunologia , AnimaisRESUMO
The human respiratory syncytial virus (RSV) is a significant health concern, particularly for infants, young children, and the elderly. This virus is known to evolve continuously due to environmental factors and herd immunity. In light of this, our study aimed to analyze the genetic variability of the G protein in RSV-A and RSV-B genotypes in Kuwait from 2020 to 2022. Between January 2020 and September 2022, we collected 490 respiratory samples from hospitalized patients with acute respiratory tract infections. These samples were tested and confirmed positive for RSV using multiplex Real-Time PCR. Subsequently, the samples underwent nucleic acid sequencing using the advanced Nanopore sequencing technology to analyze the full-length G gene. Sequence analysis showed that 64 isolates (76%) were RSV-A, and 20 isolates (24%) were RSV-B. The G genes of RSV-A belonged to genotype GA2.3.5, while all the RSV-B genotypes belonged to GB5.0.5a. New lineages and sub-lineages of RSV-A and RSV-B were detected, indicating the circulation of new strains in Kuwait. Many unique and new amino acid changes, including insertions, were found in the G proteins of Kuwaiti isolates, with the highest variability in the second hypervariable region. An increased number of N and O-linked glycosylation sites were also identified in the G protein, which could speculate to alter the antigenicity of RSV. The identified changes in the G protein of RSV-A and RSV-B genotypes might result from immune pressure and could affect the antigenic characteristics of circulating strains in Kuwait. This could potentially lead to new RSV variants that can evade the immune response. Our in-depth analysis of the G proteins of both RSV-A and RSV-B could aid in the development of more potent treatments and vaccines.
Assuntos
Variação Genética , Genótipo , Filogenia , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Kuweit , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/isolamento & purificação , Vírus Sincicial Respiratório Humano/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Glicosilação , Lactente , Pré-Escolar , Feminino , Masculino , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/imunologia , Adulto , Criança , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Adolescente , Infecções Respiratórias/virologia , Proteínas do Envelope Viral/genéticaRESUMO
Severe respiratory syncytial virus (RSV) disease is a significant contributor to the global burden of disease in infants and children. The RSV attachment protein (G) has been shown to be critical in invading airway epithelial cells through its CX3C motif interacting with the host receptor CX3CR1. The ubiquitous expression of this receptor on immune cells may explain their susceptibility to RSV infection. The RSV G protein may enhance disease severity through reprogramming of normal cellular functionality leading to inhibition of antiviral responses. While existing preventives targeting the RSV fusion (F) protein are highly effective, there are no RSV therapeutics based on the G protein to limit RSV pathogenesis. Monoclonal antibodies targeting the RSV G protein administered as post-infection therapeutics in mice have been shown to improve the antiviral response, reduce viral load and limit disease severity. Further research is required to better understand how RSV infection of immune cells contributes to pathogenesis for the development of more targeted and efficacious therapeutics.
Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Infecções por Vírus Respiratório Sincicial/metabolismo , Animais , Vírus Sincicial Respiratório Humano/imunologia , Interações Hospedeiro-Patógeno/imunologia , Receptor 1 de Quimiocina CX3C/metabolismo , Proteínas Virais de Fusão/imunologia , Proteínas Virais de Fusão/metabolismo , Camundongos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/farmacologiaRESUMO
BACKGROUND: New interventions are available for the prevention of respiratory syncytial virus (RSV) disease in young infants. We aimed to assess the potential impact and cost-effectiveness of using a long-acting monoclonal antibody (RSV mAb) or maternal RSV vaccine in the Argentine context. METHODS: We used a static proportionate outcomes model to calculate the costs and consequences of using RSV mAb or maternal RSV vaccine over a ten-year period (2025-2034) in Argentina, assuming both year-round and seasonal administration. We compared each intervention to no pharmaceutical RSV intervention. The primary outcome was the discounted cost per disability-adjusted life year (DALY) averted from a societal perspective. We assumed willingness-to-pay of US$ 12,285 per DALY averted (0.9 times the national gross domestic product per capita). We used population study data on costs and disease burden and the efficacy of clinical trials of both interventions as inputs. We ran deterministic and probabilistic uncertainty analyses. FINDINGS: Either strategy (RSV mAb or maternal RSV vaccine) could prevent >25% of RSV deaths aged <5 years and â¼30% aged <6 months (the age group where most intervention impact occurs). With a dose price of $US 50, both products have a 100% probability of being cost-effective compared to no intervention (US$ 5283 [95%CI $5203-$5363] and US$ 5522 [95%CI $5427 - $5617] per DALY averted for year-round use of RSV mAb and maternal RSV vaccine, respectively). Similar health impact could be achieved by a six-month seasonal strategy, which could improve cost-effectiveness by around 45% (assuming the dose price is unchanged). INTERPRETATION: Either RSV mAb or maternal RSV vaccine are worth consideration in Argentina when priced at ≤US$ 50 per dose. A seasonal strategy could improve cost-effectiveness.
Assuntos
Anticorpos Monoclonais , Análise Custo-Benefício , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/economia , Argentina/epidemiologia , Lactente , Vacinas contra Vírus Sincicial Respiratório/economia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Anticorpos Monoclonais/economia , Feminino , Recém-Nascido , Pré-Escolar , Masculino , Vírus Sincicial Respiratório Humano/imunologia , Anos de Vida Ajustados por DeficiênciaRESUMO
Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection amongst all ages, causing a significant global health burden. Preventative and therapeutic options for RSV infection have long been under development, and recently, several widely-publicised vaccines targeting older adult and maternal populations have become available. Promising monoclonal antibody (mAb) and antiviral (AV) therapies are also progressing in clinical trials, with the prophylactic mAb nirsevimab recently approved for clinical use in infant populations. A systematic review on current progress in this area is lacking. We performed a systematic literature search (PubMed, Embase, Web of Science, ClinicalTrials.gov, EudraCT, ANZCTR-searched Nov 29th, 2023) to identify studies on all RSV-specific mAbs and AV therapies that has undergone human clinical trials since year 2000. Data extraction focused on outcomes related to the therapeutic efficacy and safety of the intervention on trial, and all studies were graded against the OCEBM Levels of Evidence Table. Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab-YTE, nirsevimab, ALX-0171, suptavumab, clesrovimab) and 12 AV therapies (ALN-RSV01, RSV604, presatovir, MDT-637, lumicitabine, IFN-α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP-938). Of the mAbs reviewed, nirsevimab and clesrovimab hold considerable promise. The timeline for RSV-specific AV availability is less advanced, although EDP-938 and AK0529 have reported promising phase 2 efficacy and safety data. Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development. TRIAL REGISTRATION: PROSPERO registration: CRD42022376633.
Assuntos
Anticorpos Monoclonais , Antivirais , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/efeitos adversos , Anticorpos Antivirais/imunologia , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/imunologia , Ensaios Clínicos como Assunto , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Resultado do TratamentoAssuntos
Pessoal de Saúde , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vacinação , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vacinação/estatística & dados numéricos , Vírus Sincicial Respiratório Humano/imunologiaRESUMO
Respiratory syncytial virus (RSV) is the main cause of low respiratory tract infections in infants under one year of age. In the 2023/2024 season, the monoclonal antibody nirsevimab was available to protect children from RSV, and Spain has become one of the first countries worldwide to implement this strategy. It is essential to evaluate the results of this first campaign and different characteristics of the immunized population in order to plan next campaigns, especially for countries that are going to include this immunization. Our coverage was high (91.5% for those born during the season and 88.3% globally). For those born during the season, only 4.9% preferred not to immunize at the maternity hospital, which meant an average delay of 27.45 days. We observed a lower coverage in the population of immigrant origin. There was a rapid pace of immunization, since for those born before the beginning of the campaign the mean to be immunized was 15.63 days, without differences between healthy and at-risk children. This allows immunization before the RSV season (90% of the catch-up children had been immunized on November 3). The average age at which all the immunized children have received nirsevimab was lower in healthy children compared to those with risk conditions (49.65 versus 232.85 days). For those born during the campaign, the average age was also lower in healthy children (3.14 versus 14.58 days). In conclusion, we consider that the implementation of the immunization strategy with nirsevimab in the Region of Murcia, Spain, has been a success.
Assuntos
Infecções por Vírus Respiratório Sincicial , Humanos , Espanha , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Lactente , Feminino , Masculino , Programas de Imunização , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Recém-Nascido , Vírus Sincicial Respiratório Humano/imunologia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagemRESUMO
RSV infection remains a serious threat to the children all over the world, especially, in the low-middle income countries. Vaccine delivery via the mucosa holds great potential for inducing local immune responses in the respiratory tract. Previously, we reported the development of highly immunogenic RSV virus-like-particles (RSV-VLPs) based on the conformationally stable prefusogenic-F protein (preFg), glycoprotein and matrix protein. Here, to explore whether mucosal delivery of RSV-VLPs is an effective strategy to induce RSV-specific mucosal and systemic immunity, RSV-VLPs were administered via the nasal, sublingual and pulmonary routes to BALB/c mice. The results demonstrate that immunization with the VLPs via the mucosal routes induced minimal mucosal response and yet facilitated modest levels of serum IgG antibodies, enhanced T cell responses and the expression of the lung-homing marker CXCR3 on splenocytes. Immunization with VLPs via all three mucosal routes provided protection against RSV challenge with no signs of RSV induced pathology.
Assuntos
Anticorpos Antivirais , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vacinas de Partículas Semelhantes a Vírus , Proteínas Virais de Fusão , Proteínas da Matriz Viral , Animais , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Camundongos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Proteínas Virais de Fusão/imunologia , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/administração & dosagem , Feminino , Proteínas da Matriz Viral/imunologia , Proteínas da Matriz Viral/administração & dosagem , Proteínas da Matriz Viral/genética , Imunidade nas Mucosas , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Pulmão/virologia , Pulmão/imunologia , Glicoproteínas/imunologia , Glicoproteínas/administração & dosagem , Administração através da Mucosa , Vírus Sinciciais Respiratórios/imunologia , Linfócitos T/imunologiaAssuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vacinação , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Feminino , Lactente , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Gravidez , Recém-Nascido , Vírus Sincicial Respiratório Humano/imunologiaRESUMO
Through a synergistic collaboration of people with varying backgrounds and expertise, the root-cause of respiratory syncytial virus prefusion (preF) protein aggregation during freezing was identified to be supercooling. This issue was addressed through a comprehensive understanding of the product. Leveraging innovative and unconventional methods, apparatus, and approaches, it was effectively determined that key parameters influencing aggregation were the nucleation temperature and the duration of supercooling. Moreover, additional measurements revealed that a transition from the preF to the postfusion conformation occurs upon supercooling, which is likely caused by cold denaturation. The importance of considering freezing conditions is highlighted supporting analytical sampling and envisioning that better understanding of sample handling/freezing process can be applied to a wide range of protein-based products.
Assuntos
Congelamento , Agregados Proteicos , Vacinas contra Vírus Sincicial Respiratório , Vacinas contra Vírus Sincicial Respiratório/química , Vacinas contra Vírus Sincicial Respiratório/imunologia , Estabilidade de Medicamentos , Humanos , Vírus Sinciciais Respiratórios/imunologia , Estabilidade Proteica , Temperatura , Vírus Sincicial Respiratório Humano/imunologiaRESUMO
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in infants and young children worldwide. Using routine statutory health insurance claims data including patients from all regions of Germany, we investigated the health-care resource use and costs associated with RSV prophylaxis with palivizumab in Germany. In the database, infants from the birth cohorts 2015-2019 eligible for palivizumab immunization were identified using codes of the 10th revision of the International Classification of Diseases (ICD-10). Health-care resource use and costs related to immunization were determined by inpatient and outpatient administrations. Over the study period, only 1.3% of infants received at least one dose of palivizumab in their first year of life. The mean number of doses per immunized infant was 4.6. From a third-party payer perspective, the mean costs of palivizumab per infant who received at least one dose in the first year of life was 5,435 in the birth cohorts 2015-2019. Despite the substantial risk of severe RSV infection, we found low rates of palivizumab utilization. Novel preventive interventions, featuring broader indications and single-dose administration per season, contribute to mitigating the burden of RSV disease across a more extensive infant population.
Assuntos
Antivirais , Palivizumab , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/economia , Alemanha/epidemiologia , Palivizumab/administração & dosagem , Palivizumab/uso terapêutico , Lactente , Feminino , Masculino , Vírus Sincicial Respiratório Humano/imunologia , Antivirais/economia , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Custos de Cuidados de Saúde/estatística & dados numéricos , Recém-Nascido , Vacinação/estatística & dados numéricos , Vacinação/economia , Imunização/estatística & dados numéricos , Coorte de Nascimento , Pré-EscolarRESUMO
The Ad26.RSV.preF/RSV preF protein vaccine has previously demonstrated efficacyin protecting older adults against respiratory syncytial virus (RSV)-related lower respiratory tract disease in a phase 2b study. This study compared the immunogenicity of vaccine clinical trial material (CTM) representative of phase 2b clinical studies with CTM used in phase 3 clinical studies. A total of 248 adults aged 60-75 years, randomized in a 1:1 ratio, received one dose of either phase 3 CTM or phase 2b CTM. Solicited adverse events (AEs), unsolicited AEs, and serious AEs (SAEs) were assessed for 7-d, 28-d, and 6-month periods post-vaccination, respectively. RSV preF-ELISA antibody titers and RSV neutralizing titers were measured before and 14 d after vaccination. The phase 3 CTM-induced preF-ELISA response at Day 15, in terms of geometric mean titer, was shown to be non-inferior to that induced by phase 2b CTM. The RSV neutralizing antibody titers were also similar in the two groups at Day 15. The safety profile in terms of solicited AEs, unsolicited AEs, or SAEs was in general similar between the phase 3 CTM and phase 2b CTM groups, and solicited AEs were mostly mild to moderate in intensity. No related SAEs were reported, and no safety concerns were identified.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra Vírus Sincicial Respiratório , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/imunologia , Imunogenicidade da Vacina , Ensaio de Imunoadsorção Enzimática , Vírus Sincicial Respiratório Humano/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologiaRESUMO
BACKGROUND: Humoral immune response against the pre-fusion (pre-F) conformation of respiratory syncytial virus (RSV) F protein has been proposed to play a protective role against infection. An RSV pre-F maternal vaccine has been recently approved in several countries to protect young infants against RSV. We aimed to assess serum IgG titers against the pre-F and post-F conformations of RSV F protein and their association with life-threatening RSV disease (LTD) in previously healthy infants. METHODS: A prospective cohort study including hospitalized infants <12 months with a first RSV infection was conducted during 2017-2019. Patients with LTD required intensive care and mechanical respiratory assistance. RSV pre-F exclusive and post-F antibody responses were determined by post-F competition and non-competition immunoassays, respectively, and neutralizing activity was measured by plaque reduction neutralization test. RESULTS: Fifty-eight patients were included; the median age was 3.5 months and 41 % were females. Fifteen patients developed LTD. RSV F-specific antibody titers positively correlated with neutralizing antibody titers in acute and convalescent phases but, importantly, they did not associate with LTD. Acute RSV pre-F exclusive and post-F IgG titers negatively correlated with patient age (P = 0.0007 and P < 0.0001), while a positive correlation was observed between the fold changes in RSV F-specific antibody titers between convalescent and acute phase and patient age (P = 0.0014 and P < 0.0001). Infants ≤2 months exhibited significantly lower fold-changes in RSV F-specific and neutralizing antibody titers between convalescence and acute phase than older infants. Additionally, acute RSV antibody titers showed no correlation with nasal RSV load and, furthermore, nasal viral load was not associated with the development of LTD. CONCLUSIONS: This study highlights that protection against life-threatening RSV disease is not necessarily antibody-dependent. Further characterization of the immune response against RSV and its role in protection against severe disease is important for the development of the safest possible preventive strategies.