A phase 1, randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults

Abstract

Respiratory Syncytial Virus (RSV) causes lower respiratory tract infections that can be severe and sometimes fatal. The risk for severe RSV infection is highest in infants and older adults. A safe and effective RSV vaccine for older adults represents a serious unmet medical need due to higher morbidity and mortality in this age group. In this randomized, partially double-blind, placebo-controlled, phase 1 dose-escalation study, we evaluated the safety, tolerability and immunogenicity of an investigational messenger ribonucleic acid (mRNA) vaccine encoding the RSV fusion protein (F) stabilized in the prefusion conformation. The study was conducted in healthy younger adults (ages ≥18 and ≤49 years) and healthy older adults (ages ≥60 and ≤79 years). Participants received mRNA-1777 (V171) or placebo as a single intramuscular dose. For each dose level, three sentinel participants were administered open-label mRNA-1777 (V171). Seventy-two younger adults were randomized and administered 25, 100, or 200 µg mRNA-1777 (V171) or placebo, and 107 older adults were randomized and administered 25, 100, 200 or 300 µg mRNA-1777 (V171) or placebo. Primary objectives were safety and tolerability and secondary objectives included humoral and cell-mediated immunogenicity. All dose levels of mRNA-1777 (V171) were generally well tolerated and no serious adverse events related to the vaccine were reported. Immunization with mRNA-1777 (V171) elicited a humoral immune response as measured by increases in RSV neutralizing antibody titers, serum antibody titers to RSV prefusion F protein, D25 competing antibody titers to RSV prefusion F protein, and cell-mediated immune responses to RSV-F peptides.

mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge

“…When the World Health Organization declared SARS-CoV-2 a global pandemic in March 2020, Phase 1 clinical trials on the most promising vaccine candidates had already commenced. Nucleoside modified mRNA, a relatively new addition to the arsenal of vaccine platforms, has shown promise against numerous viral infectious diseases in preclinical trials (1, 2), and phase 1 and 2 trials that are completed (3, 4) or currently underway (5–7). Previous preclinical work on a related betacoronavirus enabled the rapid development of mRNA-1273, a vaccine composed of a modified mRNA encoding for a stabilized prefusion form of the SARS-CoV-2 spike (S) protein encapsulated in lipid nanoparticles (1).…”

“…Nucleoside modified mRNA, a relatively new addition to the arsenal of vaccine platforms, has shown promise against numerous viral infectious diseases in preclinical trials (1,2), and phase 1 and 2 trials that are completed (3,4) or currently underway (5)(6)(7). Previous preclinical work on (which was not certified by peer review) is the author/funder.…”

The immunogenicity and safety of respiratory syncytial virus vaccines in development: A systematic review

“…RSV F antibody increased in both the young and older age groups, and there was no serious adverse event. Thus, a further study for mRNA‐1777 in vulnerable populations is warranted 62 …”

From influenza to COVID-19: Lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases

“…Moderna's respiratory syncytial virus (RSV) candidate mRNA-1777 was generally well-tolerated in younger and older healthy adults, generating increased specific humoral and cellular immunity, but did not progress beyond Phase I [ 255 ]. However, mRNA-1345, Moderna's new RSV vaccine candidate, demonstrated a geometric mean fold rise (95% CI, relative to baseline) in RSV-A neutralizing antibody titer of nearly 8fold higher than mRNA-1777 at the same dosage level, per interim reporting in the first month post-administration in Phase I clinical trials [ 256 ].…”