Antibody development for preventing the human respiratory syncytial virus pathology

Abstract

Human respiratory syncytial virus (hRSV) is the most important etiological agent causing hospitalizations associated with respiratory diseases in children under 5 years of age as well as the elderly, newborns and premature children are the most affected populations. This viral infection can be associated with various symptoms, such as fever, coughing, wheezing, and even pneumonia and bronchiolitis. Due to its severe symptoms, the need for mechanical ventilation is not uncommon in clinical practice. Additionally, alterations in the central nervous system -such as seizures, encephalopathy and encephalitis- have been associated with cases of hRSV-infections. Furthermore, the absence of effective vaccines or therapies against hRSV leads to elevated expenditures by the public health system and increased mortality rates for the high-risk population. Along these lines, vaccines and therapies can elicit different responses to this virus. While hRSV vaccine candidates seek to promote an active immune response associated with the achievement of immunological memory, other therapies -such as the administration of antibodies- provide a protective environment, although they do not trigger the activation of the immune system and therefore do not promote an immunological memory. An interesting approach to vaccination is the use of virus-neutralizing antibodies, which inhibit the entry of the pathogen into the host cells, therefore impairing the capacity of the virus to replicate. Currently, the most common molecule targeted for antibody design against hRSV is the F protein of this virus. However, other molecular components of the virus -such as the G or the N hRSV proteins- have also been explored as potential targets for the control of this disease. Currently, palivizumab is the only monoclonal antibody approved for human use. However, studies in humans have shown a protective effect only after the administration of at least 3 to 5 doses, due to the stability of this vaccine. Furthermore, other studies suggest that palivizumab only has an effectiveness close to 50% in high-risk infants. In this work, we will review different strategies addressed for the use of antibodies in a prophylactic or therapeutic context and their ability to prevent the symptoms caused by hRSV infection of the airways, as well as in other tissues such as the CNS.

Keywords: Antibodies; Human orthopneumovirus; Passive transference; Prophylaxis; Therapy; hRSV.

Fig. 1

Timeline of antibodies therapies since the discovery of hRSV as human pathogen. Advances and implementation of different strategies that use antibodies to promote the clearance of hRSV since the virus was first discovered in 1956

Fig. 2

Development of antibody therapies against hRSV infection. The five main types of antibody therapies against the hRSV-infection are described. Also, these therapies are shown in order of development, highlighting that the only approved therapy to be used in humans to date is palivizumab. However, an interesting new possibility is also described at the end of the figure, associated with a therapy based on the use of the monoclonal anti-N-hRSV antibody