Immunogenicity and safety of a respiratory syncytial virus fusion protein (RSV F) nanoparticle vaccine in older adults

Abstract

BackgroundA preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 μg RSV F protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study.ResultsA total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine.ConclusionsRSV F protein nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.

Promising approaches for the treatment and prevention of viral respiratory illnesses

“…[159][160][161][162][163] The most advanced of these is the Novavax F-protein VLP nanoparticle vaccine with aluminum hydroxide adjuvant, which is in phase III for maternal vaccination. 129,130 Transplacental transmission of neutralizing antibodies has been demonstrated in preclinical studies, although this has not conferred significant protection from RSV. 164 Recombinant DNA vaccines are also promising because of their apparent ability to induce a balanced T H 1/T H 2 response, with a broad IgG/IgA profile mimicking live RSV challenge.…”

Clinical Features, Severity, and Incidence of RSV Illness During 12 Consecutive Seasons in a Community Cohort of Adults ≥60 Years Old

“…RSV vaccines and antivirals for older adults are currently in prelicensure clinical trials [21], and more detailed knowledge of RSV incidence and burden is needed to inform policy recommendations and evaluate cost-effectiveness. The objective of this study was to describe the clinical characteristics, severity, clinical outcomes, and long-term incidence of medically attended RSV illness in a community cohort of adults ≥60 years of age from the 2004-2005 through 2015-2016 influenza seasons.…”

Progress in the development of virus-like particle vaccines against respiratory viruses

“…It is likely that additional mutations together with DS-Cav1 or alternative mutations in RSV F will be required for further stabilization of pre-fusion F protein antigens on VLP platforms [99,100]. RSV F nanoparticle formulations of recombinant F proteins produced in the insect cell expression system are under advanced clinical trials of maternal vaccination to protect infants although the vaccine phase III clinical trial in the elderly was not successful [132,133,137]. An alternative vaccination strategy of heterologous prime with RSV pre-fusion F VLP and boost with pre-F protein nanoparticles might be a future study to develop effective and safe RSV vaccination.…”