Journal Article

Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine

Zhou, Bin, Lu, Hanxin, Kpamegan, Eloi, Boddapati, Sarathi, Raghunandan, Rama, Thomas, D. Nigel, Hickman, Somia P., Piedra, Pedro A., Glenn, Gregory M., Smith, Gale, Fries, Louis

2013

Overview

► This Phase 1 trial evaluated the safety and immunogenicity of an RSV (F) nanoparticle vaccine. ► The vaccine was well-tolerated and no related SAEs were observed. ► Both RSV A and B microneutralizating antibodies were increased in vaccinees versus placebo. ► There was a 7- to 19-fold increase in anti-F IgG and a 7- to 24-fold increase in palivizumab-like antibodies. ► The levels of immunity are similar to those seen in other settings with decreased hospitalizations. We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) protein nanoparticle vaccine. Six formulations with (5, 15, 30 and 60μg) and without (30 and 60μg) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18–49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies. The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies. The RSV F nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization. NCT01290419.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Adjuvants, Immunologic - administration & dosage / Adjuvants, Immunologic - adverse effects / Adolescent / Adult / adults / Allergy and Immunology / Aluminum Compounds - administration & dosage / Aluminum Compounds - adverse effects / Aluminum phosphate / Animals / Anti-F IgG / antibodies / Antibodies, Neutralizing - blood / Antibodies, Viral - blood / Applied microbiology / Biological and medical sciences / Biotechnology / Competitive ELISA / Female / Fundamental and applied biological sciences. Psychology / Fusion protein (F protein) / Humans / immune response / Immunogenicity / immunoglobulin G / Infections / insects / Male / Microbiology / Microneutralization / Middle Aged / Nanoparticle vaccine / Nanoparticles / Nanoparticles - administration & dosage / Nanoparticles - adverse effects / neutralization / Palivizumab / Phosphates - administration & dosage / Phosphates - adverse effects / Placebos - administration & dosage / Placebos - adverse effects / Proteins / Recombinant Fusion Proteins - administration & dosage / Recombinant Fusion Proteins - adverse effects / Recombinant Fusion Proteins - genetics / Recombinant Fusion Proteins - immunology / Respiratory syncytial virus / Respiratory syncytial virus (RSV) / Respiratory Syncytial Virus Vaccines - administration & dosage / Respiratory Syncytial Virus Vaccines - adverse effects / Respiratory Syncytial Virus Vaccines - genetics / Respiratory Syncytial Virus Vaccines - immunology / risk reduction / Sf9 Cells / SF9 insect cell / Single-Blind Method / Technology, Pharmaceutical / toxicity / Vaccines / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) / Vaccines, Synthetic - administration & dosage / Vaccines, Synthetic - adverse effects / Vaccines, Synthetic - genetics / Vaccines, Synthetic - immunology / Vaccines, Virosome - administration & dosage / Vaccines, Virosome - adverse effects / Vaccines, Virosome - genetics / Vaccines, Virosome - immunology / viruses / Young Adult