In a recent study published in Viruses, researchers evaluate the in vivo efficacy of a respiratory syncytial virus (RSV) virus-like particle (VLP) candidate vaccine in old and young rats.
Study: Development of Respiratory Syncytial Virus Vaccine Candidates for the Elderly. Image Credit: KatMoy / Shutterstock.com
Background
RSV causes acute infections in the lower respiratory tract, with infants, young children, and older adults most susceptible to RSV infections. Each year, RSV causes over 30 million infections among infants worldwide, 10% of whom require hospitalization.
Among the elderly, RSV infections can be just as severe as influenza, as it causes between 11,000 and 17,000 deaths and up to 170,000 RSV-related hospitalizations in this patient population every year. Given the wide age range of the at-risk population, RSV vaccine strategies must include varying administration protocols and formulations.
Furthermore, the durability of the vaccine in older adults also depends on immune senescence or immune aging. With RSV, there is also the possibility of multiple reinfections throughout the lifetime.
RSV has two antigenic groups denoted as A and B, both of which consist of multiple genotypes based on variations in the attachment glycoprotein (G) region. However, evidence suggests that reinfections are not always caused by differing genotypes or subtypes, with the same genotype often causing multiple reinfections. Therefore, vaccine strategies capable of producing high antibody titers are needed while also accounting for immune senescence among the elderly.
About the study
In the present study, researchers used young and elderly cotton Sigmodon hispidus rats and compared the immune responses elicited through immunization with the VLP vaccine to determine the impact of age and previous RSV infections on vaccine efficacy.
The VLP that was used as an immunogen contained the fusion glycoprotein (F) and G protein of RSV, as well as the matrix (M) and nucleocapsid (NP) core proteins from the Newcastle disease virus (NDV). The RSV G and F proteins in the VLP were present in the chimeric form and fused to the cytoplasmic and transmembrane regions of the hemagglutinin-neuraminidase (HN protein) and F protein of NDV, respectively.
Western blot assay was used to quantify G and F protein levels in the purified VLPs, whereas F protein-specific monoclonal antibodies specific were used to confirm the pre-fusion confirmation. Antibodies against the heptad repeat 2 (HR2) domain and G protein were also used for Western blot analysis to quantify RSV G and F proteins in the soluble VLP preparations.
Human epithelial (HEp-2) cell lines were used to propagate RSV, whereas plaque reduction assays were used to measure neutralizing antibody titers against RSV. The cotton rats used in the study were tested to eliminate the possibility of any pre-existing anti-RSV antibodies, as well as for antibodies against rodent viruses or paramyxoviruses. The young and elderly cohorts of cotton rats were immunized with VLP and challenged with RSV.
Lung histopathology allowed the researchers to assess peribronchiolitis, pulmonary infection, perivasculitis, alveolitis, and interstitial pneumonia. Additionally, total ribonucleic acid (RNA) was extracted from the lung tissue and used for real-time polymerase chain reaction (RT-PCR) to determine RSV gene expression. Furthermore, enzyme-linked immunosorbant assay (ELISA) was used to determine the antibody titers against the G and pre-fusion F proteins.
An effective RSV vaccine in young and old rats
Neutralizing antibody titers against RSV, as well as immunoglobulin G (IgG) levels against the RSV G and pre-F proteins, were the same in elderly and young cotton rats immunized with VLP. The level of protection elicited when challenged with RSV was also similar, thus indicating that G and F protein delivery by the VLP vaccine was successful and that the activation of immune responses is comparable for young and elderly populations.
A single dose of the VLP candidate vaccine in primed cotton rats was found to activate immune memory established during previous RSV infections and generate protective immune responses to the same extent in young and elderly cotton rats. Furthermore, comparisons of neutralizing antibody titers between cotton rats immunized at an early age or later in life revealed similar levels, thereby indicating that early vaccination against RSV would provide significant protection throughout life.
Conclusions
Immunization of young and elderly cotton rats with previous RSV infections against RSV using VLPs induced comparable levels of neutralizing antibody titers. This immunization also led to the production of IgG levels against the G and pre-F proteins, while also eliciting similar levels of protection when challenged with RSV.
Taken together, these findings suggest that previous RSV infections at an early age induce immune memory, which is efficiently activated by immunization with VLP in both young and old cotton rats.
Journal reference:
- Blanco, J. C. G., Cullen, L. M., Kamali, A., et al. (2023). Development of Respiratory Syncytial Virus Vaccine Candidates for the Elderly. Viruses 2023, 15, 1305. doi:10.3390/v15061305
Late-liver-stage malaria vaccine delivers 89% protection and boosts cellular immunity