A review of respiratory syncytial virus vaccines

A review of respiratory syncytial virus vaccines

Respiratory syncytial virus (RSV) causes respiratory diseases such as pneumonia and bronchiolitis, mainly affecting children under five years of age and older people over 65.

Lernen: Vorläufige Daten zu Boten-RNA (mRNA)-Impfstoffen gegen Respiratory Syncytial VirusDatos preliminares de las vacunas de ARN mensajero (ARNm) frente al virus respiratorio sincitial. Bildquelle: ART-ur/Shutterstock

The results of a recently published review in Vacunas examined epidemiology, molecular characteristics, populations affected by the virus and vaccines against RSV.

background

Each year, RSV infects millions of children under five and elderly people over 65, resulting in millions of hospitalizations and thousands of deaths. The disease takes the form of an epidemic in winter. Almost every child experiences at least one episode of RSV infection by the age of three; Reinfections occur either annually or every three to five years.

This shows the inadequacy of the immune system to provide long-term protection against the virus. Therefore, RSV vaccination is essential for pregnant women, children under two years of age (preferably immediately after six months of age) and the elderly population.

Molecular properties of RSV

RSV is an enveloped RNA virus from the Pneumoviridae family with ten genes encoding eleven proteins. Proteins found in the viral envelope are small hydrophobic proteins (SH), matrix proteins (M), glycoprotein F (fusion), and binding glycoproteins (G). Glycoproteins G and F confer infectivity to the virus; The former binds the virus to the host cells, and the latter facilitates its entry into the cell and leads to syncytia formation, which is pathognostic for this disease.

The G and F glycoproteins are of the immunodominant type and induce neutralizing antibodies in the host. Glycoprotein G has three types of epitopes – conserved (present in all strains), group-specific and species-specific. The precursor of glycoprotein F is inactive and contains three hydrophobic peptides - a signal peptide, a transmembrane region and a fusion peptide.

RSV has two subgroups, A and B, which circulate alternatively or together and differ antigenically by the glycoprotein G sequence. Therefore, antibodies against glycoprotein G may be subtype specific, while antibodies against glycoprotein F mostly have neutralizing activity against the two subgroups.

Generally, F glycoprotein is used as an antigen for vaccine development. This glycoprotein has two presentations (prefusion or pre-F and postfusion or post-F). Among these, the antigenic site in pre-F (“site zero”) is the strongest inducer of neutralizing antibodies.

RSV vaccination

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RSV evades host immunity through multiple mechanisms, three of which have been recognized – conformational and anatomical evasion of neutralizing antibodies and direct modulation of immunity. All of this should be taken into account when developing vaccines.

The infection caused by RSV is self-limiting – humans are the only natural reservoir. The target population of the vaccination is children under six months of age and older and older people over 65.

The developing immune system of infants is immature and unable to provide protection against exogenous antigens. Therefore, this age group constitutes a priority population for RSV vaccination; The use of monoclonal antibodies is considered the appropriate choice.

Vaccination of the mother during pregnancy is the best immunization option. In addition to transplacental transfer of antibodies, immunoglobulin A, transferred during breastfeeding, confers protection to the infant. RSV usually affects children between the ages of six months and two years. Infants and children between six months and five years form another target group; The vaccination aims to limit the circulation of the virus and its accompanying symptoms.

The third target group is the older population (65 years and older). Nearly 3-10% of all acute respiratory infections in this age group are caused by RSV, accounting for nearly 250,000 hospitalizations and 14,000 deaths annually. Additionally, waning immunity and other underlying medical conditions predispose this population to respiratory infections.

Notably, mRNA vaccines are advantageous over others due to their high safety profile, well-controllable antigen production with high antigenic identity, scalable and rapid production process, and cell culture-free production.

A non-replicative, conventional, cell-like mRNA vaccine against RSV has been developed. There are two types – unmodified mRNA and modified mRNA. These vaccines induce highly specific immune responses because they encode a single protein. However, high doses are required to induce sufficient effectiveness. To protect against rapid degradation and fragility, the mRNA molecules are also encapsulated in complex lipid structures – so-called lipid nanoparticles.

Pre-Fusion (Pre-F) has better antigenic specificity and higher affinity potential because most neutralizing antibodies target the “zero site.” Therefore, antigens that protect and maintain this epitope are preferred.

In the meantime, these vaccines pose minimal risk of side effects other than the local reaction at the injection site. Even the highest dose (300 μg) shows a low risk of side effects. Phase 1 studies confirm the immunogenicity and safety of NPL-m-RNA vaccines, while the results of phase 2 studies are awaited.

Summary

This study reviewed the epidemiology, molecular characteristics, populations affected by the virus, and vaccines against RSV. Because it has only one reservoir, it is ideal for developing a vaccine against RSV. Most vaccines use glycoprotein F (prefusion form) as the antigen. Recently, mRNA vaccines have been developed with promising antigenicity and efficacy. Further studies are warranted to examine the effectiveness of mRNA vaccines against other viruses affecting the human population.

Reference:

• Reina, J. und Fernández-Billón, M. (2022) „Vorläufige Daten zu Boten-RNA (mRNA)-Impfstoffen gegen Respiratory Syncytial Virus“, Vacunas (englische Ausgabe). doi: 10.1016/j.vacune.2022.10.007. https://www.sciencedirect.com/science/article/abs/pii/S2445146022000760

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