Mucosal vaccines against respiratory syncytial virus

Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses.

show abstract

“…165 Intranasal and oral vaccine formulations are now in the early stages of clinical studies. 166 FIG 2. Vaccine types.…”

Section: Vaccines and Mabsmentioning

confidence: 99%

Promising approaches for the treatment and prevention of viral respiratory illnesses

Papadopoulos

Megremis

Kitsioulis

et al. 2017

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…No efficient therapeutics or vaccines active against RSV are available. Only immunoprophylaxis with palivizumab, a monoclonal anti-RSV F antibody, provides some protection for infants at risk (6). Several animal models have been developed to model human RSV disease (7).…”

mentioning

confidence: 99%

Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology

Sharma

Sung

et al. 2016

J Virol

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, which causes high rates of morbidity and mortality in infants and the elderly. Models of human RSV pulmonary disease are needed to better understand RSV pathogenesis and to assess the efficacy of RSV vaccines. We assessed the RSV-specific human innate, humoral, and cellular immune responses in humanized mice (mice with a human immune system [HIS mice]) with functional human CD4 ؉ T and B cells. These mice were generated by introduction of HLA class II genes, various human cytokines, and human B cell activation factor into immunodeficient NOD scid gamma (NSG) mice by the use of an adeno-associated virus vector, followed by engraftment of human hematopoietic stem cells. During the first 3 days of infection, HIS mice lost more weight and cleared RSV faster than NSG mice. Human chemokine (C-C motif) ligand 3 (CCL3) and human interleukin-1␤ (IL-1␤) expression was detected in the RSV-infected HIS mice. The pathological features induced by RSV infection in HIS mice included peribronchiolar inflammation, neutrophil predominance in the bronchioalveolar lavage fluid, and enhanced airway mucus production. Human anti-RSV IgG and RSVneutralizing antibodies were detected in serum and human anti-RSV mucosal IgA was detected in bronchioalveolar lavage fluid for up to 6 weeks. RSV infection induced an RSV-specific human gamma interferon response in HIS mouse splenocytes. These results indicate that human immune cells can induce features of RSV lung disease, including mucus hyperplasia, in murine lungs and that HIS mice can be used to elicit human anti-RSV humoral and cellular immunity. Infection of the lower respiratory tract with respiratory syncytial virus (RSV) is the most common cause for hospitalization of infants and children (1) and globally causes up to 200,000 deaths in children under the age of 5 years (2). Premature infants, especially those with chronic lung disease or congenital heart disease (3), and the elderly (4) are the most susceptible to the development of severe disease. Early RSV infections are also associated with the later development of asthma (5). No efficient therapeutics or vaccines active against RSV are available. Only immunoprophylaxis with palivizumab, a monoclonal anti-RSV F antibody, provides some protection for infants at risk (6). Several animal models have been developed to model human RSV disease (7). As mouse models have limitations in mimicking human RSV disease, better models would be useful for the preclinical assessment of novel anti-RSV therapies and vaccines. Humoral immunity is essential in the prevention of RSV infections. Higher levels of maternally derived antibodies (8) and prophylactic administration of intravenous immunoglobulin enriched for high levels of RSV-neutralizing antibodies (9) or humanized monoclonal antibody against RSV (10) are associated with a reduction of disease severity in RSV-infected infants. Therefore, a humanized mouse model with functional human CD4 ϩ T and B...

show abstract

“…160 Furthermore, recent data indicate that 28% of preschool children who make a physician visit for wheezing receive a prescription for an antibiotic within 2 days of the visit, and 77% receive a prescription for an antibiotic within 7 days. 142,143 Unfortunately, vaccination to prevent RV infection is even more challenging due to the large number of serotypes. 160 As noted previously, bacteria (either alone or in combination with viral pathogens) have now been demonstrated to potentially play a role in acute wheezing episodes and increases in asthma symptoms in children.…”

Section: Use Of Antibiotics In Asthmamentioning

confidence: 99%