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Background: Respiratory syncytial virus (RSV) is a major cause of severe health problems in newborns and young children. The protective role and limitations of serum maternal RSV antibodies in infants under 3 months remain controversial. Methods: A two-center prospective study from 2020 to 2023 recruited infants (n=286) admitted to the respiratory departments of two children's hospitals in southwestern and southeastern China during RSV epidemic. These infants were hospitalized with lower respiratory tract infections (LRTI). We evaluated the relationship between serum RSV Prefusion (Pre-F), postfusion (Post-F) IgG levels, subtype neutralizing antibodies, and the incidence of RSV infection, as well as the relationship between these maternal antibodies and severity of disease. Since this prospective study only included data from RSV epidemic, we retrospectively reviewed medical records from the Children's Hospital of Chongqing Medical University for the years 2019 to 2023 (n=3467) to analyze population characteristics during both RSV epidemic and non-epidemic periods, using the same inclusion and exclusion criteria. Result: There were no significant differences in RSV Pre-F IgG, Post-F IgG, or RSV A or B neutralizing antibody levels between the RSV infected and non-infected groups during the epidemic. While RSV Pre-F IgG antibody was inversely correlated with disease severity, RSV Post-F IgG, and RSV A and B neutralizing antibodies did not show a similar correlation across the three illness severity categories. Additionally, there were no differences in age, gender, or illness severity distribution among hospitalized patients during epidemic and non-epidemic periods. Conclusion: Serum maternal antibody levels offer insufficient protection against RSV-associated LRTI in hospitalized infants aged 28 to 90 days. [ABSTRACT FROM AUTHOR]

Lower respiratory tract illness or disease (LRTI/LRTD) represents a significant source of morbidity and mortality following viral respiratory illnesses, yet a consensus definition for this outcome is lacking. Recent studies of novel vaccines against respiratory syncytial virus (RSV) for older adults used LRTI/LRTD as the primary outcome to assess vaccine efficacy. However, the different vaccine trials have used highly variable criteria to define this outcome, leading to difficulty in comparison of vaccine efficacy results between trials. Here we review the key differences in criteria for case definitions, highlight strategies to best approximate compatibility between definitions, and review vaccine efficacy results among currently US Food and Drug Administration (FDA)-approved vaccines using these strategies. We hope this overview will support the need to develop a consensus definition for LRTI/LRTD to improve future research related to viral respiratory disease. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and children. mRNA vaccines based on the lipopolyplex (LPP) platform have been previously reported, but they remain unapplied in RSV vaccine development. In this study, we developed a novel LPP-delivered mRNA vaccine that expresses the respiratory syncytial virus prefusion protein (RSV pre-F) to evaluate its immunogenicity and protective effect in a mouse model. We synthesized mRNAs with gene modification for RSV pre-F and prepared mRNA vaccines using the LPP delivery platform, referred to as RSV pre-F LPP-mRNA. RSV pre-F protein expression in mRNA vaccines was characterized in vitro. Then, we evaluated the effects of the immune response and protection of this mRNA vaccine in mice up to 24 weeks post-vaccination. Following booster immunization, robust and long-lasting RSV pre-F-specific IgG antibodies were detected in the serum of mice, which exhibited Th1/Th2 balanced IgG response and cross-neutralizing antibodies against different subtypes (RSV A2, B18537, and clinical isolate hRSV/C-Tan/BJ 202301), with a clear dose–response relationship observed. RSV pre-F-specific IgG antibodies were maintained in the mice for an extended period, lasting up to 18 weeks post-immunization. Concurrently, multifunctional RSV F-specific CD8+ T cells (IFN–γ, IL-2, and TNF-α) were detected in the mice. After RSV A2 challenge, the RSV pre-F LPP-mRNA vaccine led to a significant reduction in viral replication, while reduced pathological damage was observed in lung tissue. The LPP-delivered mRNA vaccine expressing RSV pre-F induces a robust and long-lasting immune response and protection, indicating good prospects for further development and application. [ABSTRACT FROM AUTHOR]

Background/Objectives: Zika virus (ZIKV) infection is associated with life-threatening diseases in humans. To date, there are no available FDA-approved therapies or vaccines for the specific treatment or prevention of ZIKV infection. Variation in the ZIKV envelope protein (Env), along with its complex quaternary structure, presents challenges to synthetic approaches for developing an effective vaccine and broadly neutralizing antibodies (bnAbs). We hypothesized that beta-cyclodextrin (BCD) could be used to uniquely inactivate infectious ZIKV without disruption of Env. Methods: ZIKV was propagated in Vero cells and admixed with BCD. The BCD-treated ZIKV was evaluated for infectivity using immunofluorescence and quantitative RT-PCR (qRT-PCR) assays, for immunoreactivity in Western blots, structural integrity by electron microscopy, and immunogenicity in mice. Results: Here, we show that 200 mM BCD-treated ZIKV is non-infectious in cell culture, remains immunoreactive with an Env-specific antibody, retains its virion shape and size, and elicits the production of immunogen-specific antibodies in immunized mice. Conclusions: These results indicate that BCD can be used to safely inactivate ZIKV, and they provide insights for vaccine and antibody development. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) causes the most common type of severe lower respiratory tract infection worldwide, and the fusion (F) protein is a target for neutralizing antibodies and vaccine development. This study aimed to investigate the immunogenicity and efficacy of an mRNA-based RSV vaccine with an F protein sequence. Methods: We designed an mRNA construct encoding a modified RSV F protein, which was further developed into an LNP-encapsulated mRNA vaccine (LVRNA007). LVRNA007 was administered to mice and cotton rats, followed by immunogenicity analysis and viral challenge studies. Protection of rodents from the viral infection was evaluated based on the presence of the virus in the lung and pathological examination of respiratory tissues. Results: LVRNA007 induced robust humoral and cellular immune responses in both mice and cotton rats, with neutralization antibody levels in the immunized animals maintained at high levels for over one year. Vaccination of LVRNA007 also protected the rodents from RSV challenge, judged by the much decreased virus titer and the pathological score in the lung tissue. In addition, no vaccine-enhanced disease (VED) phenomenon was observed with LVRNA007 vaccination. Conclusions: Based on the preclinical immunogenicity and efficacy data, LVRNA007 could be a potential promising vaccine for prophylaxis of RSV infection. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a medically important mosquito-borne orthoflavivirus, but no vaccines are currently available to prevent ZIKV-associated disease. In this study, we compared three recombinant chimeric viruses developed as candidate vaccine prototypes (rJEV/ZIKVMR-766, rJEV/ZIKVP6-740, and rJEV/ZIKVPRVABC-59), in which the two neutralizing antibody-inducing prM and E genes from each of three genetically distinct ZIKV strains were used to replace the corresponding genes of the clinically proven live-attenuated Japanese encephalitis virus vaccine SA14-14-2 (rJEV). In WHO-certified Vero cells (a cell line suitable for vaccine production), rJEV/ZIKVP6-740 exhibited the slowest viral growth, formed the smallest plaques, and displayed a unique protein expression profile with the highest ratio of prM to cleaved M when compared to the other two chimeric viruses, rJEV/ZIKVMR-766 and rJEV/ZIKVPRVABC-59, as well as their vector, rJEV. In IFNAR−/− mice, an animal model of ZIKV infection, subcutaneous inoculation of rJEV/ZIKVP6-740 caused a low-level localized infection limited to the spleen, with no clinical signs of infection, weight loss, or mortality; in contrast, the other two chimeric viruses and their vector caused high-level systemic infections involving multiple organs, consistently leading to clear clinical signs of infection, rapid weight loss, and 100% mortality. Subsequently, subcutaneous immunization with rJEV/ZIKVP6-740 proved highly effective, offering complete protection against a lethal intramuscular ZIKV challenge 28 days after a single-dose immunization. This protection was specific to ZIKV prM/E and likely mediated by neutralizing antibodies targeting ZIKV prM/E. Therefore, our data indicate that the chimeric virus rJEV/ZIKVP6-740 is a highly promising vaccine prototype for developing a safe and effective vaccine for inducing neutralizing antibody-mediated protective immunity against ZIKV. [ABSTRACT FROM AUTHOR]

African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious disease with devastating effects on the global pig industry. This warrants the development of effective control strategies, such as vaccines. However, previously developed inactivated vaccines have proven ineffective, while live‐attenuated vaccines carry inherent safety risks. The use of mRNA vaccines eliminates these risks offering a safe, cost‐effective, and efficient vaccine strategy against ASFV. In this study, a reverse vaccinology approach was used to design a multiepitope pan‐proteomic mRNA vaccine against ASFV. Various bioinformatics tools were employed to predict epitopes for cytotoxic T lymphocytes, helper T lymphocytes, and B lymphocytes. A 50S ribosomal L7/L12 protein adjuvant, 5′ cap, poly(A) tail, signal peptide, and MHC‐I‐targeting domain were incorporated into the design using appropriate linkers to increase immunogenicity, stability, and recognition efficiency. The physicochemical properties of the final construct were evaluated, and docking analyses were done with Toll‐like receptors (TLRs) 3, 4, and 7 to evaluate binding affinity. A molecular dynamics simulation was then performed to determine binding stability, while immune simulations evaluated host's immune response. Based on 100 ASFV proteomes, six epitopes that induce cytotoxic T‐cell responses, five epitopes that induce helper T‐cell responses, and four epitopes that induce antibody production were predicted. The designed vaccine construct was found to be nonallergenic, antigenic, and stable when bound to TLR4 while the binding pocket analyses of the vaccine construct to TLR3 and TLR7 indicate high translation efficiency. Immune simulations demonstrated successful induction of immune responses and generation of antigen‐specific memory cells. In conclusion, this study introduces an mRNA vaccine construct as a potential disease control strategy against ASF for in vitro confirmation. [ABSTRACT FROM AUTHOR]