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Vaccine May 2024Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last...
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last decade, and the first RSV vaccines have finally been approved in older adults and pregnant individuals. These vaccines are based on recombinant stabilized pre-fusion F glycoproteins administered as soluble proteins. Multimeric antigenic display could markedly improve immunogenicity and should be evaluated in the next generations of vaccines. Here we tested a new virus like particles-based vaccine platform which utilizes the direct fusion of an immunogen of interest to the structural human immunodeficient virus (HIV) protein Gag to increase its surface density and immunogenicity. We compared, in mice, the immunogenicity of RSV-F or hMPV-F based immunogens delivered either as soluble proteins or displayed on the surface of our VLPs. VLP associated F-proteins showed better immunogenicity and induced superior neutralizing responses. Moreover, when combining both VLP associated and soluble immunogens in a heterologous regimen, VLP-associated immunogens provided added benefits when administered as the prime immunization.
Topics: Animals; Antibodies, Neutralizing; Mice; Metapneumovirus; Vaccines, Virus-Like Particle; Female; Viral Fusion Proteins; Antibodies, Viral; Mice, Inbred BALB C; gag Gene Products, Human Immunodeficiency Virus; Respiratory Syncytial Virus, Human; Immunogenicity, Vaccine; Humans; Respiratory Syncytial Virus Vaccines; Recombinant Fusion Proteins; Respiratory Syncytial Virus Infections; Viral Vaccines
PubMed: 38641492
DOI: 10.1016/j.vaccine.2024.04.048 -
JAMA Network Open Apr 2024Respiratory syncytial virus (RSV) resurgences have been noted following the COVID-19 pandemic in many countries. Recent findings suggest that the 2021 and 2022 RSV...
IMPORTANCE
Respiratory syncytial virus (RSV) resurgences have been noted following the COVID-19 pandemic in many countries. Recent findings suggest that the 2021 and 2022 RSV seasons were more severe than in past seasons, and age distribution may have shifted toward older children in the younger than 5 years age group.
OBJECTIVES
To estimate age-specific changes in RSV hospital-based burden of disease before and after the COVID-19 pandemic and to compare incidence by Medicaid use.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included children younger than 5 years diagnosed with RSV and bronchiolitis at 50 US children's hospitals in 10 US geographic regions. The included participants had an encounter in intensive care, inpatient, emergency, or observational units, between June 1, 2015, and March 31, 2023.
EXPOSURES
Diagnosis of RSV, bronchiolitis, or both at encounter.
MAIN OUTCOME AND MEASURES
Incidence rate ratio of hospital use within each care unit before vs after the COVID-19 pandemic. It was hypothesized a priori that incidence of hospital use would increase overall in 2021 and 2022 compared with 2015 to 2019 and that the increase would be greater among children 12 months and older.
RESULTS
Of 924 061 study participants (median [IQR] age, 8 (5-16) months; 535 619 [58.0%] male), 348 077 (37.7%) were diagnosed with RSV. Of these, 187 850 (54.0%) were hospitalized. Incidence rate ratios of hospitalization increased for all ages in 2021 and 2022 compared with 2015 to 2019. Children aged 24 to 59 months were 4.86 (95% CI, 4.75-4.98) times as likely to be hospitalized in 2022 compared with 2015 to 2019, whereas infants aged 0 to 5 months were 1.77 (95% CI, 1.74-1.80) times as likely. Medicaid patients were more likely to be hospitalized than non-Medicaid patients regardless of year.
CONCLUSIONS AND RELEVANCE
Hospitalizations for RSV and bronchiolitis demonstrated atypical seasonality in 2021 and 2022, with an overall increase in RSV encounters. Postpandemic RSV hospitalization increased for all ages, but especially among older children, whereas bronchiolitis hospitalization was decreased or unchanged compared with earlier seasons. These findings suggest some of the observed increase in RSV hospital use may be due to increased testing.
Topics: Child, Preschool; Female; Humans; Infant; Male; Bronchiolitis; Cost of Illness; COVID-19; Hospitals, Pediatric; Pandemics; Respiratory Syncytial Viruses; Retrospective Studies; United States
PubMed: 38635270
DOI: 10.1001/jamanetworkopen.2024.7125 -
Frontiers in Immunology 2024Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause...
BACKGROUND
Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people.
METHODS
We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4 and CD8 T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through and studies involving healthy and diseased animal models.
RESULTS
For each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8) epitope of the F protein showed significant results of white blood cells (19.72 × 10 cells/μl), neutrophils (6.01 × 10 cells/μl), lymphocytes (12.98 × 10 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4) of the F protein substantially induced white blood cells (27.08 × 10 cells/μl), neutrophils (6.58 × 10 cells/μl), lymphocytes (16.64 × 10 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage.
CONCLUSION
In conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.
Topics: Aged; Animals; Child; Child, Preschool; Female; Humans; Infant; Mice; Antibodies, Viral; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Epitopes, T-Lymphocyte; Granzymes; Immunoglobulin G; Peptides; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 38629077
DOI: 10.3389/fimmu.2024.1349749 -
Canadian Family Physician Medecin de... Apr 2024
Topics: Humans; Aged; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 38627002
DOI: 10.46747/cfp.7004258 -
BMJ Open Apr 2024Respiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk...
Rationale and protocol for a prospective cohort study of respiratory viral infections in patients admitted from emergency departments of community hospitals: Effect of respiratory Virus infection on EmeRgencY admission (EVERY) study.
INTRODUCTION
Respiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk conditions and older adults. However, the relationship between RSV or other incidental respiratory infections and acute exacerbations of underlying conditions has not been well investigated. The primary objective of this study is to estimate RSV prevalence, risk factors for adverse outcomes or hospitalisation and their effect on the hospital course of patients with acute respiratory symptoms admitted from emergency departments. Furthermore, we evaluate the prevalence of other respiratory viruses associated with respiratory symptoms.
METHODS AND ANALYSIS
We are conducting a multicentre prospective cohort study in Japan. We plan to enrol 3000 consecutive patients admitted from emergency departments with acute respiratory symptoms or signs from 1 July 2023 to 30 June 2024. A nasopharyngeal swab is obtained within 24 hours of admission and the prevalence of RSV and other respiratory viruses is measured using the FilmArray Respiratory 2.1 panel. Paired serum samples are collected from patients with suspected lower respiratory infections to measure RSV antibodies at admission and 30 days later. Information on patients' hospital course is retrieved from the electronic medical records at discharge, death or 30 days after admission. Furthermore, information on readmission to the hospital and all-cause mortality is collected 180 days after admission. We assess the differences in clinical outcomes between patients with RSV or other respiratory viruses and those without, adjusting for baseline characteristics. Clinical outcomes include in-hospital mortality, length of hospital stay, disease progression, laboratory tests and management of respiratory symptoms or underlying conditions.
ETHICS AND DISSEMINATION
The study protocol was approved by the institutional review boards of participating hospitals. Our study reports will be published in academic journals as well as international meetings.
TRIAL REGISTRATION NUMBER
NCT05913700.
Topics: Humans; Aged; Respiratory Syncytial Virus Infections; Prospective Studies; Hospitals, Community; Hospitalization; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Emergency Service, Hospital
PubMed: 38626982
DOI: 10.1136/bmjopen-2023-081037 -
Influenza and Other Respiratory Viruses Apr 2024Human respiratory syncytial virus (RSV) is one of the most frequent causes of respiratory infections in children under 5 years of age, but its socioeconomic impact and...
INTRODUCTION
Human respiratory syncytial virus (RSV) is one of the most frequent causes of respiratory infections in children under 5 years of age, but its socioeconomic impact and burden in primary care settings is still little studied.
METHODS
During the 2022/2023 winter season, 55 pediatricians from five Italian regions participated in our community-based study. They collected a nasal swab for RSV molecular test from 650 patients under the age of 5 with acute respiratory infections (ARIs) and performed a baseline questionnaire. The clinical and socioeconomic burden of RSV disease in primary care was evaluated by two follow-up questionnaires completed by the parents of positive children on Days 14 and 30.
RESULTS
RSV laboratory-confirmed cases were 37.8% of the total recruited ARI cases, with RSV subtype B accounting for the majority (65.4%) of RSV-positive swabs. RSV-positive children were younger than RSV-negative ones (median 12.5 vs. 16.5 months). The mean duration of symptoms for all children infected by RSV was 11.47 ± 6.27 days. We did not observe substantial differences in clinical severity between the two RSV subtypes, but RSV-A positive patients required more additional pediatric examinations than RSV-B cases. The socioeconomic impact of RSV infection was considerable, causing 53% of children to be absent from school, 46% of parents to lose working days, and 25% of families to incur extra costs.
CONCLUSIONS
Our findings describe a baseline of the RSV disease burden in primary care in Italy before the introduction of upcoming immunization strategies.
Topics: Humans; Child; Infant; Child, Preschool; Respiratory Syncytial Virus Infections; Seasons; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Italy; Cost of Illness; Primary Health Care; Hospitalization
PubMed: 38622776
DOI: 10.1111/irv.13282 -
Human Vaccines & Immunotherapeutics Dec 2024Influenza remains a public health threat, partly due to suboptimal effectiveness of vaccines. One factor impacting vaccine effectiveness is strain mismatch, occurring... (Review)
Review
Influenza remains a public health threat, partly due to suboptimal effectiveness of vaccines. One factor impacting vaccine effectiveness is strain mismatch, occurring when vaccines no longer match circulating strains due to antigenic drift or the incorporation of inadvertent (eg, egg-adaptive) mutations during vaccine manufacturing. In this review, we summarize the evidence for antigenic drift of circulating viruses and/or egg-adaptive mutations occurring in vaccine strains during the 2011-2020 influenza seasons. Evidence suggests that antigenic drift led to vaccine mismatch during four seasons and that egg-adaptive mutations caused vaccine mismatch during six seasons. These findings highlight the need for alternative vaccine development platforms. Recently, vaccines based on mRNA technology have demonstrated efficacy against SARS-CoV-2 and respiratory syncytial virus and are under clinical evaluation for seasonal influenza. We discuss the potential for mRNA vaccines to address strain mismatch, as well as new multi-component strategies using the mRNA platform to improve vaccine effectiveness.
Topics: Humans; Influenza Vaccines; mRNA Vaccines; Seasons; Influenza, Human; RNA, Messenger; Respiratory Syncytial Virus, Human
PubMed: 38619079
DOI: 10.1080/21645515.2024.2336357 -
Influenza and Other Respiratory Viruses Apr 2024Pneumonia is a leading cause of morbidity and mortality in children < 5 years. We describe nasopharyngeal carriage of respiratory syncytial virus (RSV), human...
Predictors of Respiratory Syncytial Virus, Influenza Virus, and Human Metapneumovirus Carriage in Children Under 5 Years With WHO-Defined Fast-Breathing Pneumonia in Pakistan.
BACKGROUND
Pneumonia is a leading cause of morbidity and mortality in children < 5 years. We describe nasopharyngeal carriage of respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus among children with fast-breathing pneumonia in Karachi, Pakistan.
METHODS
We performed a cross-sectional analysis of nasopharyngeal swabs from children aged 2-59 months with fast-breathing pneumonia, enrolled in the randomized trial of amoxicillin versus placebo for fast-breathing pneumonia (RETAPP) (NCT02372461) from 2014 to 2016. Swabs were collected using WHO standardized methods, processed at the Aga Khan University, Pakistan. Viral detection was performed using LUMINEX xTAG respiratory viral panel assay and logistic regression identified clinical and sociodemographic predictors.
FINDINGS
Of the 1000 children tested, 92.2% (n = 922) were positive for viral carriage. RSV, hMPV, and influenza virus were detected in 59 (6.4%), 56 (6.1%), and 58 (6.3%) children and co-infections in three samples (two RSV-hMPV and one influenza-hMPV). RSV carriage was common in infants (56%), we observed a higher occurrence of fever in children with hMPV and influenza virus (80% and 88%, respectively) and fast breathing in RSV (80%) carriage. RSV carriage was positively associated with a history of fast/difficulty breathing (aOR: 1.96, 95% CI 1.02-3.76) and low oxygen saturation (aOR: 2.52, 95% CI 1.32-4.82), hMPV carriage was positively associated with a complete vaccination status (aOR: 2.22, 95% CI 1.23-4.00) and body temperature ≥ 37.5°C (aOR: 2.34, 95% CI 1.35-4.04) whereas influenza viral carriage was associated with body temperature ≥ 37.5°C (aOR: 4.48, 95% CI 2.53-7.93).
CONCLUSION
We observed a high nasopharyngeal viral carriage among children with WHO-defined fast-breathing pneumonia in Pakistan. Fever, difficulty in breathing, hypoxia and vaccination status are important clinical predictors for viral nonsevere community-acquired pneumonia.
Topics: Child; Child, Preschool; Humans; Infant; Cross-Sectional Studies; Fever; Influenza, Human; Metapneumovirus; Orthomyxoviridae; Pakistan; Respiratory Syncytial Virus, Human; World Health Organization
PubMed: 38616564
DOI: 10.1111/irv.13285 -
Vaccine May 2024Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B),... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B), is licensed for prevention of RSV-associated lower respiratory tract illness (LRTI) in older adults and for maternal vaccination for prevention of RSV-associated LRTI in infants. To support licensure and large-scale manufacturing, this lot consistency study was conducted to demonstrate equivalence in immunogenicity across 3 RSVpreF lots.
METHODS
This phase 3, multicenter, parallel-group, placebo-controlled, randomized (1:1:1:1), double-blind study evaluated immunogenicity, safety, and tolerability of RSVpreF in healthy 18-49-year-old adults. Participants received a single 120-µg injection of 1 of 3RSVpreF lots or placebo. Geometric mean ratio (GMR) of RSV serum 50 % neutralizing geometric mean titers obtained 1 month after vaccination were compared between each vaccine lot for RSV A and RSV B, separately. Equivalence between lots was defined using a 1.5-fold criterion (GMR 95 % CIs for every lot pair within the 0.667-1.5 interval). Safety and tolerability were assessed.
RESULTS
Of 992participants vaccinated, 948 were included in the evaluable immunogenicity population. All 3 RSVpreF lots elicited strong immune responses, meeting the 1.5-fold equivalence criterion for all between-lot comparisons for both RSV A and RSV B. Across the 3 lots, RSV A and RSV B 50 % neutralizing geometric mean titers substantially increased from baseline (RSV A, 1671-1795; RSV B 1358-1429) to 1 month after RSVpreF vaccination (RSV A, 24,131-25,238; RSV B, 19,238-21,702), corresponding to ≥14-fold increases in 50 % neutralizing titers for both RSV A and RSV B from before to 1 month after vaccination. Single doses of RSVpreF were safe and well tolerated, with similar safety profiles across the 3 RSVpreF lots.
CONCLUSIONS
These findings support the reproducibility of RSVpreF vaccine manufacturing with similar safety and reactogenicity profiles (NCT05096208).
Topics: Humans; Respiratory Syncytial Virus Vaccines; Female; Male; Adult; Double-Blind Method; Young Adult; Adolescent; Antibodies, Viral; Middle Aged; Respiratory Syncytial Virus Infections; Immunogenicity, Vaccine; Respiratory Syncytial Virus, Human; Antibodies, Neutralizing; Vaccines, Subunit; Healthy Volunteers; Vaccination; Viral Fusion Proteins
PubMed: 38616438
DOI: 10.1016/j.vaccine.2024.03.070 -
Euro Surveillance : Bulletin Europeen... Apr 2024Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary...
Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI: 91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.
Topics: Adult; Humans; Influenza, Human; COVID-19; Respiratory Syncytial Virus, Human; Europe; Seasons; Respiratory Syncytial Virus Infections
PubMed: 38606570
DOI: 10.2807/1560-7917.ES.2024.29.15.2400178