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Pediatric Annals Mar 2024
Topics: Humans; Immunization; Vaccination; Respiratory Syncytial Virus, Human
PubMed: 38466331
DOI: 10.3928/19382359-20240214-01 -
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 -
The Journal of Infectious Diseases Nov 2023Type I interferon receptor knockout (IFNAR-/-) mice are not able to generate a complete innate immune response; therefore, these mice are often considered to assess the...
Type I interferon receptor knockout (IFNAR-/-) mice are not able to generate a complete innate immune response; therefore, these mice are often considered to assess the pathogenicity of emerging viruses. We infected IFNAR-/- mice with a low or high dose of Lloviu virus (LLOV) or Bombali virus (BOMV) by the intranasal (IN) or intraperitoneal (IP) route and compared virus loads at early and late time points after infection. No signs of disease and no viral RNA were detected after IN infection regardless of LLOV dose. In contrast, IP infections resulted in increased viral loads in the high-dose LLOV and BOMV groups at the early time point. The low-dose LLOV and BOMV groups achieved higher viral loads at the late time point. However, there was 100% survival in all groups and no signs of disease. In conclusion, our results indicate a limited value of the IFNAR-/- mouse model for investigation of the pathogenicity of LLOV and BOMV.
Topics: Animals; Mice; Mice, Knockout; Receptor, Interferon alpha-beta; Virulence; Ebolavirus; Immunity, Innate; Interferon Type I
PubMed: 37352146
DOI: 10.1093/infdis/jiad226 -
The Lancet. Microbe Dec 2023
Topics: Humans; Henipavirus; Henipavirus Infections; Nervous System Physiological Phenomena
PubMed: 37804851
DOI: 10.1016/S2666-5247(23)00295-1 -
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 -
The Lancet. Microbe Mar 2024
Topics: Animals; Humans; Nipah Virus; Public Health; Zoonoses; Henipavirus Infections
PubMed: 38141635
DOI: 10.1016/S2666-5247(23)00361-0 -
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 -
Emerging Microbes & Infections Dec 2023Viral RNA synthesis of several non-segmented, negative-sense RNA viruses (NNSVs) takes place in inclusion bodies (IBs) that show properties of liquid organelles, which...
Viral RNA synthesis of several non-segmented, negative-sense RNA viruses (NNSVs) takes place in inclusion bodies (IBs) that show properties of liquid organelles, which are formed by liquid-liquid phase separation of scaffold proteins. It is believed that this is driven by intrinsically disordered regions (IDRs) and/or multiple copies of interaction domains, which for NNSVs are usually located in their nucleo - and phosphoproteins. In contrast to other NNSVs, the Ebola virus (EBOV) nucleoprotein NP alone is sufficient to form IBs without the need for a phosphoprotein, and to facilitate the recruitment of other viral proteins into these structures. While it has been proposed that also EBOV IBs are liquid organelles, this has so far not been formally demonstrated. Here we used a combination of live cell microscopy, fluorescence recovery after photobleaching assays, and mutagenesis approaches together with reverse genetics-based generation of recombinant viruses to study the formation of EBOV IBs. Our results demonstrate that EBOV IBs are indeed liquid organelles, and that oligomerization but not IDRs of the EBOV nucleoprotein plays a key role in their formation. Additionally, VP35 (often considered the phosphoprotein-equivalent of EBOV) is not essential for IB formation, but alters their liquid behaviour. These findings define the molecular mechanism for the formation of EBOV IBs, which play a central role in the life cycle of this deadly virus.
Topics: Humans; Ebolavirus; Hemorrhagic Fever, Ebola; Inclusion Bodies; Nucleoproteins; Phosphoproteins
PubMed: 37306660
DOI: 10.1080/22221751.2023.2223727 -
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