Abstract
BackgroundHuman respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract. Currently, there is no clinically approved vaccine against RSV infection. Recent studies have shown that helper-dependent adenoviral (HDAd) vectors may represent effective and safe vaccine vectors. However, viral challenge has not been investigated following mucosal vaccination with HDAd vector vaccines.MethodsTo explore the role played by HDAd as an intranasally administered RSV vaccine vector, we constructed a HDAd vector encoding the codon optimized fusion glycoprotein (Fsyn) of RSV, designated HDAd-Fsyn, and delivered intranasally HDAd-Fsyn to mice.ResultsRSV-specific humoral and cellular immune responses were generated in BALB/c mice, and serum IgG with neutralizing activity was significantly elevated after a homologous boost with intranasal (i.n.) application of HDAd-Fsyn. Humoral immune responses could be measured even 14 weeks after a single immunization. Immunization with i.n. HDAd-Fsyn led to effective protection against RSV infection on challenge.ConclusionThe results indicate that HDAd-Fsyn can induce powerful systemic immunity against subsequent i.n. RSV challenge in a mouse model and is a promising candidate vaccine against RSV infection.
Highlights
Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract [1,2] and causes significant illness in the elderly and adults with underlying risk factors such as immunodeficiency [3,4]
We report that the helper-dependent adenoviral (HDAd)-fusion glycoprotein (Fsyn) vaccine candidate induces both a serum antibody response and an RSV-specific CD8+ T-cell response
Characterization of antibody responses induced by HDAd-Fsyn Serum antibody responses play vital roles in protection against RSV infection [1]
Summary
Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract [1,2] and causes significant illness in the elderly and adults with underlying risk factors such as immunodeficiency [3,4]. Two live attenuated and a viral vector vaccine, have been evaluated in seronegative infants and seropositive. Ad5-vector vaccines encoding RSV antigens can be administered in Ad5-seronegative children aged between 6 and 24 months, when maternal antibodies have declined substantially and a rapid increase in Ad5 seroprevalence from natural infections is absent [11]. It would have a major impact on morbidity by preventing a first or second RSV infection in these infants [1]. Viral challenge has not been investigated following mucosal vaccination with HDAd vector vaccines
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