Induction of protective effector immunity to prevent pathogenesis caused by the respiratory syncytial virus. Implications on therapy and vaccine design

Abstract

SummaryHuman respiratory syncytial virus (hRSV) is the leading cause of respiratory illness in infants and young children around the globe. This pathogen, which was discovered in 1956, continues to cause a huge number of hospitalizations due to respiratory disease and it is considered a health and economic burden worldwide, especially in developing countries. The immune response elicited by hRSV infection leads to lung and systemic inflammation, which results in lung damage but is not efficient at preventing viral replication. Indeed, natural hRSV infection induces a poor immune memory that allows recurrent infections. Here, we review the most recent knowledge about the lifecycle of hRSV, the immune response elicited by this virus and the subsequent pathology induced in response to infection in the airways. Novel findings about the alterations that this virus causes in the central nervous system and potential therapies and vaccines designed to treat or prevent hRSV infection are discussed.

Past, Present and Future Approaches to the Prevention and Treatment of Respiratory Syncytial Virus Infection in Children

“…Indeed, one of the challenges to maternal vaccination is the timing: depending on the time of year in which a third trimester vaccination occurs there is a risk that any conferred immunity may not last throughout the infant’s first RSV season [ 142 ]. It is expected that passive immunization continues during the breastfeeding period, protecting the infant from early and recurrent infections [ 164 ]. However, any vaccine administered to pregnant women will need to meet high tolerability and safety standards [ 165 ].…”

The role of Th17 and Treg responses in the pathogenesis of RSV infection

“…Vaccines currently under investigation should promote protective and efficient immunity without adverse effects, prevent the Th2 immune response demonstrated upon FI-RSV vaccination, and promote viral clearance before disease establishment (94). However, up to now, no efficient vaccine has been licensed (93).…”

“…Another approach using the bacillus Calmette-Guérin bacteria modified to express RSV's N and M2-1 proteins was able to induce the beneficial Th1 response and resulted in a decrease of pulmonary inflammation and reduced viral loads. As a last example, a subunit vaccine using RSV's F protein was able to elicit a Th1 response in mice as well (94).…”

Recombinant BCG Vaccines Reduce Pneumovirus-Caused Airway Pathology by Inducing Protective Humoral Immunity

“…Some reports have suggested that the host immune system is unable to generate an effective and protective immunological memory against either of these viruses, which after disease resolution, prompts the acquisition of repeated infections throughout life (18, 19). Accordingly, it has been described that the nucleoprotein of hRSV (N-hRSV) is able to inhibit the assembly of an effective immunological synapse, apparently by clustering with the pMHC-TCR complex (20).…”