INTRODUCTION:

Respiratory Syncytial Virus (RSV) is a leading cause of respiratory illness, particularly in vulnerable populations such as infants and the elderly¹. RSV vaccination efforts aim to mitigate the impact of the virus and prevent severe outcomes². This review critically analyzes the developmental landscape of RSV vaccines, focusing on potential benefits, challenges, and future prospects.³

Respiratory syncytial virus (RSV) infection represents an excellent paradigm of precision medicine in modern paediatrics and several clinical trials are currently performed in the prevention and management of RSV infection⁴. A new taxonomic terminology for RSV was recently adopted, while the diagnostic and omics techniques have revealed new modalities in the early identification of RSV infections and for better understanding of the disease pathogenesis⁵.

This review article presents the key messages of the plenary lectures, oral presentations and posters of the ‘5th workshop on paediatric virology’ (Sparta, Greece, 12th October 2019) organized by the Paediatric Virology Study Group, focusing on recent advances in the epidemiology, pathogenesis, diagnosis, prognosis, clinical management and prevention of RSV infection in childhood⁶.

RSV Vaccination

OBJECTIVE:

This review aims to:

1. Assess the advancements in RSV vaccine research.

2. Analyze the potential benefits and challenges associated with RSV vaccines.

3. Explore avenues for future research and public health initiatives.

4. Investigate the role of herd immunity and community-level protection in RSV prevention.

5. Evaluate the seasonal variability of RSV outbreaks and its implications for optimal vaccination timing.

6. Provide recommendations for targeted vaccination strategies, considering high-risk populations and global disparities.

7. Assess the current statistical data on efficacy, safety, and outcomes of RSV vaccine candidates.

METHODS:

A systematic review of scientific literature, ongoing clinical trials, and health organization reports was conducted. Key search terms included RSV vaccine development, efficacy, safety, and public health implications⁷

With the exception of virus-vector subunit vaccines, subunit vaccines are under development for RSV-primed older children and adults. Virus vector vaccines are under development for both⁸. The goal for a subunit vaccine is to safely, induce a more effective immune response than natural infection. One or both of RSV proteins that induce neutralizing antibodies (F and G) are likely required for an effective subunit vaccine⁹. Proteins that induce T cell immunity (N, M2-1, and other proteins). Co-expression of the M protein and P proteins produces RSV virus-like-particle (VLPs) vaccine platform¹⁰.

Schematic structure of RSV (Figure.1)

The virus envelope contains the fusion protein (F), the small hydrophobic protein (SH) and the attachment protein (G). Underlying the envelope is the matrix protein (M). The nucleocapsid consists of single-stranded RNA (ss RNA) encapsulated by the nucleoprotein (N). Associated with the nucleocapsid are the RNA polymerase (L) and the phosphoprotein (P). RSV, respiratory syncytial virus (shown in fig.1). ¹⁸

Function and Role of RSV Proteins in Vaccine Design:

All RSV proteins are included in design of one or more vaccines. Understanding the role of RSV proteins in the biology of infection and disease pathogenesis helps determine if, and how, individual proteins might contribute to a vaccine¹¹.

NS1 and NS2 Proteins:

NS1 is a 139 aa and NS2 is a 124 a non-structural proteins, i.e., not incorporated into the virus but produced during transcription and replication¹². They both participate in virus replication and antagonize host innate responses designed to control infection. Deleting or codon de-optimizing he gene ability to alter host cell responses that control the infection that reduces virus replication and attenuates the virus¹³.

N Protein:

The 391-amino acid N protein binds to and encapsidates the viral RNA generating an RNAse resistant nucleocapsid that is the template for transcription and replication of RSV genome¹⁴. N also inhibits host cell down regulation of cellular and viral protein production and may impair dendritic cell and T cell interactions¹⁵.

P Protein:

The P protein is a 214 a protein that is part of the ribonucleoprotein complex (RNP). The P protein interacts with both the N and L proteins and is an essential co-factor for L function. P also interacts with the M2-1 protein¹⁶.

M Protein:

The M protein is 256 aa and guides assembly, budding, and virion formation. It lines the inner surface of the viral envelop, helps determine the shape of virus particles, and, with P, forms VLP¹⁷.

SH Protein:

The SH, small hydrophobic protein is 64-65 a amino acid type II protein located on the surface of the virus. It forms a pentameric cation-selective ion channel, or a viroporin, and can activate NLRP3 inflammasome leading to IL-1b expression¹⁸.

G Protein:

The G protein is a class II protein of amino acids (AA) long. The extracellular domain contains a variable, highly glycosylated domain and a central conserved domain (CCD-G) followed by a second variable, highly glycosylated domain. Within the CCD-G are 13 aa conserved among all strains and a CX3C chemokine motif. Through the CX3C motif, G, like the one CX3C chemokine, fractalkine, binds to the chemokine receptor CX3CR1. G, as does F, also binds to cell surface glycosaminoglycans (GAGs) through its heparin binding domains and GAGs are one receptor for RSV infection¹⁹.

Overview of RSV Vaccination:

Several RSV vaccine candidates, employing various technologies, are in development, targeting diverse age groups and high-risk populations. Live attenuated viruses, subunit vaccines, and mRNA technologies are utilized to combat RSV²⁰.

Benefits:

Prevention of RSV Infections: Vaccines aim to reduce the incidence of RSV infections, particularly in vulnerable populations.

Reduced Severity of Illness: Clinical trial data suggests vaccinated individuals experience milder symptoms, potentially lowering the overall disease burden.

Herd Immunity: Widespread vaccination could establish herd immunity, protecting vulnerable individuals and creating a community-level defense against RSV outbreaks²¹.

Effectiveness:

Phase II and III clinical trials demonstrate encouraging efficacy rates, showcasing a significant decrease in both symptomatic and severe RSV cases among vaccinated individuals²².

Safety:

While generally well-tolerated, mild side effects, including local reactogenicity and transient systemic symptoms, have been reported. Continued monitoring through post-marketing surveillance is essential²³.

Challenges:

Age-specific Considerations: Balancing maternal immunization for passive protection in infants and direct vaccination for older populations poses challenges²⁴.

Seasonal Variability: The seasonal nature of RSV outbreaks presents challenges for optimal vaccination timing and distribution logistics²⁵.

Several challenges to clinical development of RSV vaccines were noted by both academia and industry. Perhaps the biggest challenge is identifying clinically meaningful and reproducible indicators of vaccine impact on severity of disease, both for infants and for the elderly²⁶.

Statistical Data:

Efficacy rates of leading RSV vaccine candidates range from 70% to 90% in preventing symptomatic RSV infections.

Severe RSV cases among vaccinated individuals are reduced by approximately 50% compared to unvaccinated individuals²⁷.

Current Status:

Multiple RSV vaccine candidates are in advanced clinical trials, with regulatory submissions anticipated in the coming years. Initial distribution plans are being formulated, showcasing a positive trajectory toward the introduction of RSV vaccines into the market²⁸.

CONCLUSION:

The imminent introduction of RSV vaccines underscores a significant step forward in addressing the public health impact of RSV. Challenges such as age-specific considerations and seasonal variability require careful attention, emphasizing the need for targeted vaccination strategies and robust surveillance systems.

Stakeholders and policymakers must develop access pathways once new agents are available to reduce the burden of infections and hospitalizations.

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Received on 26.03.2024 Modified on 03.06.2024

Research J. Science and Tech. 2024; 16(3):265-269.

DOI: 10.52711/2349-2988.2024.00037