The phase 1 clinical trial to test the safety and immune response of an experimental nasal spray vaccine designed to provide broader protection against emerging COVID-19 variants.

RT’s Three Key Takeaways: 

  1. A phase 1 trial is currently enrolling healthy adults at three sites in the United States to test the safety of an experimental nasal vaccine designed to provide enhanced protection against emerging variants of SARS-CoV-2. 
  2. This investigational vaccine, MPV/S-2P, aims to reduce SARS-CoV-2 infections and transmission by delivering the vaccine directly to the respiratory tract where natural coronavirus infections begin.
  3. The trial, sponsored by the NIH and led by Hana M. El Sahly, MD, at Baylor College of Medicine, will enroll 60 adult participants who have previously received at least three doses of an FDA-approved or -authorized mRNA COVID-19 vaccine. Participants will be divided into three cohorts to receive different dosages of the nasal spray vaccine. Over a year, scientists will monitor vaccine tolerance and immune response in both blood and nasal mucosal tissues.

A phase 1 trial testing the safety of an experimental nasal vaccine that may provide enhanced breadth of protection against emerging variants of SARS-CoV-2, the virus that causes COVID-19, is now enrolling healthy adults at three sites in the United States. 

The National Institutes of Health (NIH) is sponsoring the first-in-human trial of the investigational vaccine, which was designed and tested in pre-clinical studies by scientists from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Laboratory of Infectious Diseases.

“The rapid development of safe and effective COVID-19 vaccines was a triumph of science, and their use greatly mitigated the toll of the pandemic,” says NIAID director Jeanne M. Marrazzo, MD, MPH, in a release. “While first-generation COVID-19 vaccines continue to be effective at preventing severe illness, hospitalizations, and death, they are less successful at preventing infection and milder forms of disease. With the continual emergence of new virus variants, there is a critical need to develop next-generation COVID-19 vaccines, including nasal vaccines, that could reduce SARS-CoV-2 infections and transmission.”

Study Design and Objectives

The study aims to enroll 60 adult participants, ages 18 to 64 years old, who previously received at least three prior doses of an FDA-approved or -authorized mRNA COVID-19 vaccine. The trial sites are Baylor College of Medicine, Houston; The Hope Clinic of Emory University, Decatur, Georgia; and New York University, Long Island. Hana M. El Sahly, MD, at the Baylor College of Medicine Vaccine Research Center, is leading the study.

Study volunteers will be divided into three cohorts. Those in the first cohort will receive one dose of the investigational vaccine delivered in a nasal spray at the lowest dosage, with enrollees in the next two cohorts receiving progressively higher doses. During seven follow-up visits over about one year, scientists will measure how well the vaccine candidate is tolerated, and if it generates an immune response in the blood and in the nose.

The investigational vaccine, MPV/S-2P, uses murine pneumonia virus (MPV) as a vector to deliver a version of the SARS-CoV-2 spike protein (S-2P) stabilized in its prefusion conformation. MPV does not cause disease in humans or non-human primates but does have an affinity for epithelial cells that line the respiratory tract and may be effective in delivering vaccine to the places where natural coronavirus infections begin.

Pre-Clinical Findings and Project NextGen

In pre-clinical non-human primate studies, MPV/S-2P was safe and well tolerated. It produced robust systemic immune responses, including SARS-CoV-2-directed antibodies, as well as local immunity in cells in the mucosal tissues lining the nose and respiratory tract. Studies in humans and animals suggest that mucosal immunity is more effective than systemic immunity in controlling replication of respiratory viruses.

This is the first NIAID clinical trial to be conducted as part of the US Department of Health and Human Services (HHS) Project NextGen. Led by the Biomedical Advanced Research and Development Authority, part of the HHS Administration for Strategic Preparedness and Response, and NIAID, Project NextGen is a coordinated effort between the federal government and the private sector to broaden the pipeline of new, innovative vaccines and therapeutics. 

Through Project NextGen, NIAID plans to facilitate clinical development of next-generation COVID-19 vaccines in phase 1 and 2 trials.

Photo caption: Colorized scanning electron micrograph of a cell (blue) infected with the Omicron strain of SARS-CoV-2 virus particles (pink), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility in Fort Detrick, Maryland.

Photo credit: NIAID