Approved and developed passive and active immunization against respiratory syncytial virus in childhood and pregnancy

In a recent study published in Journal of Pediatricsresearchers examined active and passive vaccination of children against respiratory syncytial virus (RSV).

Background

Despite the worldwide importance of RSV infections in children, only one monoclonal antibody, Palivizumab, has been approved for therapeutic use to date. However, in the next few years, improvements in RSV immunology may allow the production of safe and effective new vaccinations and monoclonal antibodies.

Overall strategy

In this study, researchers summarized the available information on licensed and developing active and passive RSV vaccines for children and pregnant women.

The growing understanding of the immune response to RSV and the growing recognition of the disease burden of RSV have resulted in a substantial increase in the number of suitable candidates for passive and active vaccination. A combination of techniques such as passive and active immunization is the optimal strategy for primary protection of newborns and preschoolers.

For infants less than six months of age, maternal immunization of pregnant women involves protein-based vaccines containing either stabilized prefusion (pre-F) glycoprotein subunits of glycoprotein vaccines or virus-like particles containing protein F. The primary technique for older children is active vaccination with live vaccines, including attenuated virus, recombinant vector-based vaccines or chimeric vaccines.

Active childhood vaccination

Live attenuated vaccine

This is one of the most promising families of vaccines for newborns and older children, as they have been designed to generate a strong immune response through attenuated local infection through stimulation of the cellular and humoral immune systems. Nine candidates are currently in clinical trials.

Notably, in one analysis involving seven phases, one study of 239 infants aged 6 to 24 months evaluated five vaccines in development that elicited neutralizing antibody responses in 80% of vaccinated subjects. Efficacy in reducing RSV episodes in acute respiratory illness requiring medical treatment was 67%, with an 88% reduction in RSV-related lower respiratory tract infections (LRTIs).

Recombinant viral vector vaccines

This category of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines consists of viruses with replication-deficient RSV genes and is widely used. It is intended to stimulate cellular and humoral immunity. For children, the main choice is pre-F.Ad26.RSV, which uses an adenoviral vector to express the pre-fusion F protein. The results of a phase 2 study on RSV-seropositive infants in the second year of life showed that pre-F. Ad26.RSV was immunogenic and safe.

Chimeric vaccine

The production of RSV protein in bacteria or viruses with better safety characteristics and antigen presentation than vector-based vaccination is a defining feature of this vaccine line. A possible option based on intradermal administration of recombinant BCG N protein has demonstrated safety and immunogenicity in a phase 1 study in healthy subjects. A second potential candidate is Sendai virus (SeV)-RSV, which efficiently replicates the gene carrying the RSV F protein. In phase 1 studies where this vaccine was administered intranasally to healthy subjects, its safety was demonstrated.

vaccine mRNA

Phase 1 research of the mRNA-1345 vaccine encoding stabilized pre-F RSV is now underway in healthy women of reproductive age, RSV-seropositive children between 12 and 59 months of age, and the elderly. Another advantage is that RSV mRNA vaccination can be paired with mRNA vaccines that are also being investigated in adults against influenza and SARS-CoV-2.

Passive immunization

Palivizumab is the only monoclonal antibody clinically approved and used in the last three decades. The efficacy and safety of palivizumab have been demonstrated in three randomized and placebo-controlled clinical trials. A meta-analysis of 2,831 high-risk neonates revealed that palivizumab use was not associated with an increased likelihood of adverse events, but was associated with a decrease in RSV-related hospitalizations and pediatric intensive care unit admissions.

Nirsevimab is the most promising of the new monoclonal antibodies with a long half-life as evidenced by phase 3 studies. In 2020, a placebo-controlled phase 2b clinical trial evaluated nirsevimab in 1,453 healthy preterm infants who were born between 29 and 34 gestational days. week and day 6, and saw a 78.4% reduction in the odds of an RSV hospitalization that was sustained. for 150 days after vaccination. Clesrovimab (MK-1654) is also a potential monoclonal antibody that, like nirsevimab, targets the IV site of the F protein.

Conclusion

Overall, the study highlighted that effective active vaccination against RSV is expected to become a reality in future years. Nevertheless, in the meantime, monoclonal antibodies continue to be used in high-risk populations in most countries.