A Phase 2 randomized, observer-blind, placebo-controlled, dose-ranging trial of aluminum-adjuvanted respiratory syncytial virus F particle vaccine formulations in healthy women of childbearing age

Allison August; Gregory M Glenn; Eloi Kpamegan; Somia P Hickman; Dewal Jani; Hanxin Lu; D Nigel Thomas; Judy Wen; Pedro A Piedra; Louis F Fries

doi:10.1016/j.vaccine.2017.05.045

A Phase 2 randomized, observer-blind, placebo-controlled, dose-ranging trial of aluminum-adjuvanted respiratory syncytial virus F particle vaccine formulations in healthy women of childbearing age

Vaccine. 2017 Jun 27;35(30):3749-3759. doi: 10.1016/j.vaccine.2017.05.045. Epub 2017 Jun 1.

Authors

Allison August¹, Gregory M Glenn², Eloi Kpamegan³, Somia P Hickman⁴, Dewal Jani⁵, Hanxin Lu⁶, D Nigel Thomas⁷, Judy Wen⁸, Pedro A Piedra⁹, Louis F Fries¹⁰

Affiliations

¹ Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: [email protected].
² Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: [email protected].
³ Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: [email protected].
⁴ Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: [email protected].
⁵ Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: [email protected].
⁶ Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: [email protected].
⁷ Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: [email protected].
⁸ Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: [email protected].
⁹ Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: [email protected].
¹⁰ Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD 20878, USA. Electronic address: [email protected].

PMID: 28579233
DOI: 10.1016/j.vaccine.2017.05.045

Abstract

Objective: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules.

Methods: Placebo, or vaccine with 60μg or 120μg RSV F protein and 0.2, 0.4, or 0.8mg aluminum, were administered intramuscularly on Days 0 and 28 to healthy women 18-35years old. Immunogenicity was assessed from Days 0 through 91 based on anti-F IgG and palivizumab-competitive antibody (PCA) by ELISA, and RSV A and B neutralizing antibodies by microneutralization (MN) assay. Solicited adverse events were collected through Day 7 and unsolicited adverse events through Day 91.

Results: All formulations were well-tolerated, with no treatment-related serious adverse events. Anti-F IgG and PCA responses were correlated and increased after both doses, while MN increased significantly only after the first dose, then plateaued. The timeliest and most robust antibody responses followed one dose of 120μg RSV F protein and 0.4mg aluminum, but persistence through 91days was modestly (∼25%) superior following two doses of 60μg RSV F protein and 0.8mg aluminum. Western blot analysis showed RSV infections in active vaccinees were reduced by 52% overall (p=0.009 overall) over the Day 0 through 90 period.

Conclusions: RSV F nanoparticle vaccine formulations were well tolerated and immunogenic. The optimal combination of convenience and rapid response for immunization in the third trimester occurred with 120μg RSV F and 0.4mg aluminum, which achieved peak immune responses in 14days and sufficient persistence through 91days to allow for passive transfer of IgG antibodies to the fetus. NCT01960686.

Keywords: Maternal immunization, transplacental antibody transfer; Neutralizing antibody; Palivizumab-competitive antibody; RSV vaccine; anti-F immunoglobulin G (IgG).

Publication types

Clinical Trial, Phase II
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic*
Adolescent
Adult
Antibodies, Neutralizing / blood
Antibodies, Viral / blood
Dose-Response Relationship, Immunologic
Female
Humans
Immunogenicity, Vaccine
Immunoglobulin G / blood
Pregnancy
Pregnancy Complications, Infectious / prevention & control
Respiratory Syncytial Virus Infections / immunology
Respiratory Syncytial Virus Infections / prevention & control*
Respiratory Syncytial Virus Vaccines / administration & dosage*
Respiratory Syncytial Virus Vaccines / adverse effects
Respiratory Syncytial Virus Vaccines / immunology*
Vaccines, Virus-Like Particle / administration & dosage
Vaccines, Virus-Like Particle / adverse effects
Vaccines, Virus-Like Particle / genetics
Vaccines, Virus-Like Particle / immunology*
Viral Fusion Proteins / administration & dosage
Viral Fusion Proteins / immunology*
Young Adult

Substances

Adjuvants, Immunologic
Antibodies, Neutralizing
Antibodies, Viral
F protein, human respiratory syncytial virus
Immunoglobulin G
Respiratory Syncytial Virus Vaccines
Vaccines, Virus-Like Particle
Viral Fusion Proteins

Associated data

ClinicalTrials.gov/NCT01960686