title: Recombinant low-seroprevalent adenoviral vectors Ad26 and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against RSV infection in cotton rats.
abstract: RSV is an important cause of lower respiratory tract infections in children, the elderly and in those with underlying medical conditions. Although the high disease burden indicates an urgent need for a vaccine against RSV, no licensed RSV vaccine is currently available. We developed an RSV vaccine candidate based on the low-seroprevalent human adenovirus serotypes 26 and 35 (Ad26 and Ad35) encoding the RSV fusion (F) gene. Single immunization of mice with either one of these vectors induced high titers of RSV neutralizing antibodies and high levels of F specific interferon-gamma-producing T cells. A Th1-type immune response was indicated by a high IgG2a/IgG1 ratio of RSV-specific antibodies, strong induction of RSV-specific interferon-gamma and tumor necrosis factor-alpha cytokine producing CD8 Tcells, and low RSV-specific CD4 T-cell induction. Both humoral and cellular responses were increased upon a boost with RSV-F expressing heterologous adenovirus vector (Ad35 boost after Ad26 prime or vice versa). Both single immunization and prime-boost immunization of cotton rats induced high and long-lasting RSV neutralizing antibody titers and protective immunity against lung and nasal RSV A2 virus load up to at least 30 weeks after immunization. Cotton rats were also completely protected against challenge with a RSV B strain (B15/97) after heterologous prime-boost immunization. Lungs from vaccinated animals showed minimal damage or inflammatory infiltrates post-challenge, in contrast to animals vaccinated with formalin-inactivated virus. Our results suggest that recombinant human adenoviral Ad26 and Ad35 vectors encoding the RSV F gene have the potential to provide broad and durable protection against RSV in humans, and appear safe to be investigated in infants.
authors: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands. Electronic address: MWidjojo@its.jnj.com.
authors: Myra N
authors: MN
authors: Widjojoatmodjo
authors: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors: Lies
authors: L
authors: Bogaert
authors: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors: Bob
authors: B
authors: Meek
authors: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors: Roland
authors: R
authors: Zahn
authors: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors: Jort
authors: J
authors: Vellinga
authors: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors: Jerome
authors: J
authors: Custers
authors: Janssen Research & Development, Beerse, Belgium.
authors: Jan
authors: J
authors: Serroyen
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors: Katarina
authors: K
authors: Radošević
authors: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors: Hanneke
authors: H
authors: Schuitemaker
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D007109:Immunity; D007114:Immunization; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000235:genetics* / Q000276:immunology*; D016205:Sigmodontinae; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins
keywords: Ad26; Ad35; Adenovirus vector; RSV fusion protein; Respiratory syncytial virus; Vaccine