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Clinical and Experimental Immunology Dec 2023Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of... (Review)
Review
Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of protection. Increasing evidence suggests that Fc-mediated antibody effector functions have an important role, but little is known about the development, heterogeneity, and durability of these functional responses. In light of future vaccine strategies, a clear view of the immunological background and differences between various target populations is of crucial importance. In this study, we have assessed both quantitative and qualitative aspects of RSV-specific serum antibodies, including IgG/IgA levels, IgG subclasses, antibody-dependent complement deposition, cellular phagocytosis, and NK cell activation (ADNKA). Samples were collected cross-sectionally in different age groups (11-, 24-, and 46-month-old children, adults, and older adults; n = 31-35 per group) and longitudinally following natural RSV infection in (older) adults (2-36 months post-infection; n = 10). We found that serum of 24-month-old children induces significantly lower ADNKA than the serum of adults (P < 0.01), which is not explained by antibody levels. Furthermore, in (older) adults we observed boosting of antibody levels and functionality at 2-3 months after RSV infection, except for ADNKA. The strongest decrease was subsequently observed within the first 9 months, after which levels remained relatively stable up to three years post-infection. Together, these data provide a comprehensive overview of the functional landscape of RSV-specific serum antibodies in the human population, highlighting that while antibodies reach adult levels already at a young age, ADNKA requires more time to fully develop.
Topics: Infant; Child; Humans; Aged; Child, Preschool; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Antibodies, Viral; Immunoglobulin G; Antibodies, Neutralizing
PubMed: 37605554
DOI: 10.1093/cei/uxad101 -
Pediatric Annals Mar 2024
Topics: Humans; Immunization; Vaccination; Respiratory Syncytial Virus, Human
PubMed: 38466331
DOI: 10.3928/19382359-20240214-01 -
Antiviral Research Feb 2024The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with... (Review)
Review
The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with comorbidities. Sixty-seven years have passed since the discovery of hRSV, and only a few successful mitigation or treatment tools have been developed against this virus. One of these is immunotherapy with monoclonal antibodies against structural proteins of the virus, such as Palivizumab, the first prophylactic approach approved by the Food and Drug Administration (FDA) of the USA. In this article, we discuss different strategies for the prevention and treatment of hRSV infection, focusing on the molecular mechanisms against each target that underly the rational design of antibodies against hRSV. At the same time, we describe the latest results regarding currently approved therapies against hRSV and the challenges associated with developing new candidates.
Topics: Infant; Child; Humans; Aged; Respiratory Syncytial Virus, Human; Antiviral Agents; Palivizumab; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal
PubMed: 38145755
DOI: 10.1016/j.antiviral.2023.105783 -
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 -
Current Opinion in Infectious Diseases Apr 2024To highlight the respiratory syncytial virus (RSV) disease burden and the current developments and challenges in RSV prevention for older adults ≥60 years through... (Review)
Review
PURPOSE OF REVIEW
To highlight the respiratory syncytial virus (RSV) disease burden and the current developments and challenges in RSV prevention for older adults ≥60 years through analysis of RSV epidemiology and the effectiveness of emerging vaccines.
RECENT FINDINGS
In industrialized countries, RSV incidence rates and hospitalization rates among older adults are estimated to be 600.7 cases per 100 000 person-years and 157 hospitalizations per 100 000 person-years, respectively. Yet, accurately determining RSV morbidity and mortality in older adults is challenging, thus resulting in substantially under-estimating the disease burden. The in-hospital fatality rates vary substantially with age and geographies, and can be as high as 9.1% in developing countries. Two promising RSV vaccines for the elderly have been approved, demonstrating efficacies of up to 94.1%, signifying considerable advancement in RSV prevention. However, concerns over potential side effects remain.
SUMMARY
RSV is associated with a significant burden in older adults. While the landscape of RSV prevention in older adults is promising with the licensure of vaccines from two companies, current trial data underscore the need for additional studies. Addressing the real-world effectiveness of these vaccines, understanding potential rare side effects, and ensuring broad inclusivity in future trials are crucial steps to maximize their potential benefits.
Topics: Humans; Infant; Aged; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Hospitalization; Cost of Illness; Vaccines
PubMed: 38197402
DOI: 10.1097/QCO.0000000000001000 -
Clinical Infectious Diseases : An... Dec 2023We reviewed hospital-onset respiratory viral infections, 2015-2023, in one hospital to determine whether Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)... (Review)
Review
We reviewed hospital-onset respiratory viral infections, 2015-2023, in one hospital to determine whether Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission prevention measures prevented non-SARS-CoV-2 respiratory viral infections. Masking, employee symptom attestations, and screening patients and visitors for symptoms were associated with a 44%-53% reduction in hospital-onset influenza and respiratory syncytial virus (RSV), accounting for changes in community incidence.
Topics: Humans; SARS-CoV-2; Incidence; COVID-19; Influenza, Human; Hospitals; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Respiratory Tract Infections
PubMed: 37531616
DOI: 10.1093/cid/ciad451 -
Cellular and Molecular Life Sciences :... Feb 2024The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed... (Review)
Review
The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed that it may also engender severe complications in the context of viral respiratory disease. Here, we review the mechanisms of complement activation and regulation and explore their roles in both protecting against infection and exacerbating disease. We discuss emerging evidence related to complement-targeted therapeutics in COVID-19 and compare the role of the complement in other respiratory viral diseases like influenza and respiratory syncytial virus. We review recent mechanistic studies and animal models that can be used for further investigation. Novel knockout studies are proposed to better understand the nuances of the activation of the complement system in respiratory viral diseases.
Topics: Animals; Humans; COVID-19; Pandemics; Complement System Proteins; Influenza, Human; Respiratory Syncytial Virus, Human
PubMed: 38368584
DOI: 10.1007/s00018-024-05157-8 -
Obstetrics and Gynecology Apr 2024Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide with peak hospitalization rates for RSV-mediated illnesses between 2... (Review)
Review
Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide with peak hospitalization rates for RSV-mediated illnesses between 2 and 3 months of life. Until very recently, prevention strategies for RSV involved primarily passive immunization of neonates at high risk with monoclonal antibodies and promotion of breastfeeding. The Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices now recommends passive immunization of all neonates with monoclonal antibodies during RSV season, and the American Association of Pediatrics has endorsed this practice. The U.S. Food and Drug Administration (FDA) recently approved a vaccination for RSV in pregnancy. The CDC's Advisory Committee on Immunization Practices has recently recommended RSV vaccination for all pregnant patients between 32 and 36 weeks of gestation who are anticipated to deliver during RSV season if they are not planning nirsevimab for their infants. This recommendation has been endorsed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine. In this clinical perspective, we review the scientific evidence, potential concerns, challenges, and future considerations for RSV vaccination in pregnancy.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; Antibodies, Monoclonal; Immunization; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; United States; Vaccination; Practice Guidelines as Topic
PubMed: 38330405
DOI: 10.1097/AOG.0000000000005524 -
Viral Immunology 2024The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a... (Review)
Review
The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine.
Topics: Child; Humans; Middle Aged; Aged; Respiratory Syncytial Virus Vaccines; Antibodies, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Vaccines
PubMed: 38315746
DOI: 10.1089/vim.2023.0093 -
The Lancet. Microbe Aug 2023
Topics: Humans; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 37390835
DOI: 10.1016/S2666-5247(23)00195-7