Étude de l'infectiosité, de l'innocuité et de l'immunogénicité de deux vaccins recombinants, vivants atténués, à vecteur B/HPIV3 exprimant la glycoprotéine de fusion du HMPV administrée par pulvérisation nasale aux enfants séropositifs au HPIV3 de 24 à 24 ans

Inclusion Criteria:

• ≥24 months of age and <60 months of age at the time of inoculation
• HAI Screening for HPIV3-neutralizing antibody is obtained within the calendar year of inoculation
• Seropositive for HPIV3 antibody, defined as serum HPIV3 HAI titer >1:8
• Pre-inoculation serum sample for HPIV3-neutralizing antibody specimen is obtained no more than 42 days prior to inoculation
• In good health based on review of the medical record, history, and physical examination at the time of inoculation
• Received routine immunizations appropriate for age based on the Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
• Growing normally for age as demonstrated on a World Health Organization (WHO) growth chart, AND has a current height and weight above the 3rd percentile for age
• Expected to be available for the duration of the study
• Parent/guardian is willing and able to provide written informed consent

Exclusion Criteria:

• <24 months of age and >60 months of age at the time of inoculation.

• Born at less than 34 weeks gestation

• Maternal history of a positive HIV test before or during pregnancy.

• Evidence of chronic disease

• Known or suspected infection or impairment of immunological functions

• Bone marrow/solid organ transplant recipient

• Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities

• Suspected or documented developmental disorder, delay, or other developmental problem

• Cardiac abnormality requiring treatment

• Lung disease or reactive airway disease

• More than one episode of medically diagnosed wheezing in the first year of life

• Wheezing episode or received bronchodilator therapy or racemic epinephrine within the past 12 months

• Wheezing episode or received bronchodilator therapy after the age of 12 months

• Previous receipt of supplemental oxygen therapy in a home setting

• Previous receipt of an investigational HPIV3 or HMPV vaccine

• Previous receipt or planned administration of human immunoglobulin within the past 6 months. Receipt of licensed monoclonal antibody products for passive prophylaxis against RSV (e.g., nirsevimab) within the past 6 months is not a cause for exclusion

• Previous receipt of any blood products within the past 6 months.

• Previous anaphylactic reaction

• Previous vaccine-associated adverse reaction that was Grade 3 or above.

• Known hypersensitivity to any study product component

• Member of a household that contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation

• Member of a household that, at the date of inoculation through the 10th day after inoculation, contains an immunocompromised individual including but not limited to:

  • a person who is HIV-infected
  • a person who has cancer and has received chemotherapy within the 12 months prior to enrollment
  • a person living with a solid organ or bone marrow transplant

• Attends a daycare facility that does not separate children by age and contains a child <12 months of age at the date of inoculation through the 10th day after inoculation

• Receipt of any of the following prior to enrollment:

  • inactivated influenza vaccine within 3 days prior, or
  • any other inactivated vaccine, messenger RNA (mRNA) vaccine, or live-attenuated rotavirus vaccine within the 14 days prior, or
  • any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
  • another investigational vaccine or investigational drug within 28 days prior, or
  • salicylate (aspirin) or salicylate-containing products within the past 28 days

• Scheduled administration of any of the following after planned inoculation:

  • inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
  • any live vaccine other than rotavirus within the 28 days after, or
  • any salicylate or salicylate-containing products within the 28 days after, or
  • another investigational vaccine or investigational drug in the 56 days after

• Receipt of any of the following medications within 3 days prior to study enrollment:

  • systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
  • intranasal medications, or
  • other prescription medications except the permitted concomitant medications listed below
  • Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents

• Any of the following events at the time of enrollment:

  • fever (temporal or rectal temperature of ≥100.4°F), or
  • upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis), or
  • nasal congestion significant enough to interfere with successful inoculation, or
  • otitis media, or
  • contact with a person diagnosed with COVID-19 disease or active SARS-CoV-2 infection within the preceding 10 days