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A novel RSV vaccine that could possibly be effective across all ages

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A novel RSV vaccine that could possibly be effective across all ages

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 young and old rats.

Study: Development of Respiratory Syncytial Virus Vaccine Candidates for the Elderly. Image Credit: KatMoy / Shutterstock.com

Background

RSV causes acute infections within the lower respiratory tract, with infants, young children, and older adults most at risk of RSV infections. Annually, RSV causes over 30 million infections amongst infants worldwide, 10% of whom require hospitalization.

Among the many elderly, RSV infections could be just as severe as influenza, because it causes between 11,000 and 17,000 deaths and as much as 170,000 RSV-related hospitalizations on this patient population yearly. Given the wide age range of the at-risk population, RSV vaccine strategies must include various administration protocols and formulations.

Moreover, the sturdiness of the vaccine in older adults also depends upon immune senescence or immune aging. With RSV, there may be also the opportunity of multiple reinfections throughout the lifetime.

RSV has two antigenic groups denoted as A and B, each of which consist of multiple genotypes based on variations within the attachment glycoprotein (G) region. Nonetheless, evidence suggests that reinfections are usually not at all times brought on by differing genotypes or subtypes, with the identical genotype often causing multiple reinfections. Due to this fact, vaccine strategies capable of manufacturing high antibody titers are needed while also accounting for immune senescence among the many elderly.

In regards to the study

In the current study, researchers used young and elderly cotton Sigmodon hispidus rats and compared the immune responses elicited through immunization with the VLP vaccine to find out the impact of age and former RSV infections on vaccine efficacy.

The VLP that was used as an immunogen contained the fusion glycoprotein (F) and G protein of RSV, in addition to the matrix (M) and nucleocapsid (NP) core proteins from the Newcastle disease virus (NDV). The RSV G and F proteins within the VLP were present within 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 within the purified VLPs, whereas F protein-specific monoclonal antibodies specific were used to verify the pre-fusion confirmation. Antibodies against the heptad repeat 2 (HR2) domain and G protein were also used for Western blot evaluation to quantify RSV G and F proteins within 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 utilized in the study were tested to eliminate the opportunity of any pre-existing anti-RSV antibodies, in addition to 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 evaluate peribronchiolitis, pulmonary infection, perivasculitis, alveolitis, and interstitial pneumonia. Moreover, total ribonucleic acid (RNA) was extracted from the lung tissue and used for real-time polymerase chain response (RT-PCR) to determine RSV gene expression. Moreover, enzyme-linked immunosorbant assay (ELISA) was used to find out the antibody titers against the G and pre-fusion F proteins.

An efficient RSV vaccine in young and old rats

Neutralizing antibody titers against RSV, in addition to immunoglobulin G (IgG) levels against the RSV G and pre-F proteins, were the identical in elderly and young cotton rats immunized with VLP. The extent 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 identical extent in young and elderly cotton rats. Moreover, 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 supply 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 each 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

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