AI Article Synopsis
- Researchers have focused on creating a safer and more effective vaccine for respiratory syncytial virus (RSV) by optimizing the formalin concentration to preserve a key protein (pre-F) on the virus.
- The study involved treating RSV with various formalin concentrations, leading to a vaccine (opti-FI-RSV) that showed better immune response in mice and rats without causing harmful effects.
- The findings highlight the importance of using the right adjuvants alongside the opti-FI-RSV vaccine to enhance immune responses and prevent issues like enhanced respiratory disease (ERD).
Article Abstract
Background: Despite considerable efforts toward vaccine development in past decades, no effective vaccines against respiratory syncytial virus (RSV) are available. Recently, we showed that an optimized formalin concentration can preserve prefusion protein (pre-F) on RSV-infected cells and protect mice against RSV infection without causing enhanced respiratory disease (ERD). Here, we sought to further stabilize pre-F on RSV virions by optimizing the production of FI-RSV.
Methods: Freshly produced RSV virions were treated with formalin under different concentrations to obtained an opti-FI-RSV vaccine with high pre-F level. Immunogenicity and safety of opti-FI-RSV were evaluated in Balb/c mice and cotton rats.
Results: Using 0.0156-0.1778% formalin, we successfully preserved pre-F on virions. This opti-FI-RSV exhibited improved immunogenicity and efficacy without causing ERD. Surprisingly, opti-FI-RSV, with a pre-F-dominant immunogen, still caused ERD after immunization with a suboptimal dose or when the neutralizing antibody titers declined. ERD was avoided by coadministering opti-FI-RSV with CpG + MPLA adjuvant, which subsequently induced a Th1-biasing immune response and, more importantly, significantly improved antibody avidity.
Conclusions: Our study provides a new method to obtain a novel FI-RSV vaccine with a high pre-F level and may provide a reference for developing other inactivated vaccines. Our findings also emphasize that appropriate adjuvants are critical for nonreplicating vaccines.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612074 | PMC |
| http://dx.doi.org/10.3390/v14102085 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular (i.m.
View Article and Find Full Text PDFA Historical Perspective on Respiratory Syncytial Virus Prevention: A Journey Spanning Over Half a Century From the Setback of an Inactive Vaccine Candidate to the Success of Passive Immunization Strategy.
J Pediatric Infect Dis Soc
July 2024
NYU Grossman Long Island School of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases, NYU Grossman Long Island School of Medicine, Mineola, NY, USA.
The efforts to prevent respiratory syncytial virus (RSV) infection in infants span over half a century. RSV vaccine development began in the 1960s, and it confronted a significant disappointment after testing a formalin-inactivated RSV (FI RSV) vaccine candidate. This inactivated RSV vaccine was not protective.
View Article and Find Full Text PDFPathogenicity and virulence of human respiratory syncytial virus: Multifunctional nonstructural proteins NS1 and NS2.
Virulence
November 2023
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Human respiratory syncytial virus (hRSV) is a major cause of acute lower respiratory tract infections in children under the age of two as well as in the elderly and immunocompromised worldwide. Despite its discovery over 60 years ago and the global impact on human health, limited specific and effective prophylactic or therapeutic options have been available for hRSV infections. Part of the lack of treatment options is attributed to the legacy of vaccine failure in the 1960s using a formalin-inactivated RSV (FI-RSV), which led to enhancement of disease post exposure to hRSV infection and hampered subsequent development of vaccine candidates.
View Article and Find Full Text PDFGamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F Protein.
Microbiol Spectr
August 2023
Accelerator Radioisotope Research Section, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea.
Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes lower respiratory diseases among infants and elderly people. Moreover, formalin-inactivated RSV (FI-RSV) vaccine induces serious enhanced respiratory disease (ERD). Radiation has been investigated as an alternative approach for producing inactivated or live-attenuated vaccines, which enhance the antigenicity and heterogeneous protective effects of vaccines compared with conventional formalin inactivation.
View Article and Find Full Text PDFMycobacterium bovis BCG Given at Birth Followed by Inactivated Respiratory Syncytial Virus Vaccine Prevents Vaccine-Enhanced Disease by Promoting Trained Macrophages and Resident Memory T Cells.
J Virol
March 2023
Department of Immunology, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Respiratory syncytial virus (RSV) infects more than 60% of infants in their first year of life. Since an experimental formalin-inactivated (FI) RSV vaccine tested in the 1960s caused enhanced respiratory disease (ERD), few attempts have been made to vaccinate infants. ERD is characterized by Th2-biased responses, lung inflammation, and poor protective immune memory.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!