New Developments and Challenges in Antibody-Based Therapies for the Respiratory Syncytial Virus

Abstract

Since the discovery of the human respiratory syncytial virus (hRSV), multiple research efforts have been conducted to develop vaccines and treatments capable of reducing the risk of severe disease, hospitalization, long-term sequelae, and death from this pathogen in susceptible populations. In this sense, therapies specifically directed against hRSV are mainly based on monoclonal and polyclonal antibodies such as intravenous IgG (IVIG)-RSV and the monoclonal antibody palivizumab. However, these therapies are associated with significant limitations, including the need for the recruitment of a high number of convalescent volunteers who donate blood to procure IVIG-RSV and the costs associated with the need for repeated administrations of palivizumab. These limitations render this product not cost-effective for populations other than high-risk patients. These problems have underscored that it is still necessary to identify new safe and effective therapies for human use. However, these new therapies must benefit from a comparatively cheap production cost and the opportunity to be available to the high-risk population and anyone who requires treatment. Here, we review the different antibodies used to prevent the pathology caused by hRSV infection, highlighting therapies currently approved for human use and their clinical value. Also, the new, most promising candidates based on preclinical studies and clinical trial results are revised.

Recent Progress toward the Discovery of Small Molecules as Novel Anti-Respiratory Syncytial Virus Agents

“…Moreover, achieving global high immunization rates poses challenges related to cost and accessibility, particularly in resource-constrained settings. The need for booster doses due to RSV seasonality to ensure long-term immunity after vaccination or passive immunization warrants careful attention. , Additionally, in the context of maternal vaccination, determining the optimal timing for maximum potency remains an area requiring further investigation. In parallel, it is important to consider the lack of vaccines for older infants and children who are unable to benefit from these immunization strategies. , Lastly, monitoring resistance development is critical, especially considering documented cases of palivizumab-resistant RSV strains.…”

“…The need for booster doses due to RSV seasonality to ensure longterm immunity after vaccination or passive immunization warrants careful attention. 196,197 Additionally, in the context of maternal vaccination, determining the optimal timing for maximum potency remains an area requiring further investigation. In parallel, it is important to consider the lack of vaccines for older infants and children who are unable to benefit from these immunization strategies.…”

Fc-mediated functions and the treatment of severe respiratory viral infections with passive immunotherapy – a balancing act

“…Prophylactic administration of RSV-IVIG to children and infants with bronchopulmonary dysplasia and/or prematurity reduced the incidence of lower respiratory tract infections and hospitalisations ( 63 , 64 ), but there is no conclusive evidence to support a role for RSV-IVIG in treatment of severe RSV ( 65 , 66 ). RSV-IVIG was prone to unpredictable efficacy profiles and was replaced by palivizumab ( 58 ), which neutralizes RSV with a potency ~50 times greater than RSV-IVIG ( 60 , 67 ). Palivizumab and nirsevimab are administered intramuscularly and indicated for prophylaxis only ( 58 , 59 ).…”

“…RSV-IVIG was prone to unpredictable efficacy profiles and was replaced by palivizumab ( 58 ), which neutralizes RSV with a potency ~50 times greater than RSV-IVIG ( 60 , 67 ). Palivizumab and nirsevimab are administered intramuscularly and indicated for prophylaxis only ( 58 , 59 ).…”

Independent Analysis of the Results of the First Infant Immunization Campaign with Beyfortus® (Nirsevimab, Monoclonal Antibody against RSV, Bronchiolitis Virus): Mixed Results, Identification of Biases and Possible Role and Mechanisms of ADE (Antibody Dependent Enhancement)

“…In infants, the immune response to RSV is polarized towards a Th2 profile, leading to considerable inflammation of the lungs. To date, no research favoring a vaccine with a Th1 response has been successful [6]. The development of RSV vaccines has been hampered by the results of the inactivated vaccine, which caused deaths from vaccine-antibody-enhanced RSV disease (VAERD -Vaccine-associated enhanced respiratory disease, a form of ADE, antibody-dependent enhancement): the mechanism of VAERD is classically associated with an exaggerated Th2 response, high levels of non-neutralizing antibodies, low levels of neutralizing antibodies and the presence of eosinophils in the pulmonary epithelium [7].…”