Vaccines for Respiratory Infections in Children

Recruiting at 3 trial locations

Overseen By Suzanne Woods, CCRP, CRNP-P

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Salicylates, Intranasal medications

Disqualifiers: Chronic disease, Lung disease, Wheezing, others

Compensation: Varies

Number of Visits: 10

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of two new vaccines for respiratory infections in children. These vaccines, named B/HPIV3/HMPV-F-B365 and B/HPIV3/HMPV-PreF-A, target viruses that can cause breathing issues, especially in children who have previously had such infections. Participants will receive either one of the vaccines or a placebo (a harmless substitute) without knowing which they received. Children with past respiratory infections and antibodies for these viruses might be suitable candidates. The study routine includes daily temperature checks, regular check-ins, and a few clinic visits. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive these new vaccines.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before and after enrollment. You must avoid certain vaccines, salicylate products, and specific medications like antibiotics and antivirals for a set period before and after the trial. However, some medications like nutritional supplements and topical treatments are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have shown that the B/HPIV3/HMPV-F-B365 vaccine targets specific respiratory viruses, potentially helping to protect against infections. The B/HPIV3/HMPV-PreF-A vaccine also did not raise major safety concerns in children who received it. For both vaccines, researchers reported no serious side effects in the children studied, indicating they were generally well-tolerated.

As these are Phase 1 studies, the primary goal is to assess the safety of these vaccines. Scientists continue to collect information, but so far, the vaccines appear safe for young children. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these vaccines for respiratory infections in children because they introduce a novel approach to prevention. Unlike traditional vaccines that may require injections, both the B/HPIV3/HMPV-F-B365 and B/HPIV3/HMPV-PreF-A vaccines are administered intranasally with the Vax300 VaxINator atomization device, making them potentially more comfortable and easier to administer, especially for kids. Additionally, these vaccines target multiple respiratory viruses at once, which could offer broader protection compared to current vaccines that typically focus on a single virus. This innovative delivery method and the multi-targeted approach hold promise for enhancing the effectiveness and convenience of respiratory infection prevention in children.

What evidence suggests that this trial's vaccines could be effective for respiratory infections in children?

This trial will compare the B/HPIV3/HMPV-F-B365 vaccine and the B/HPIV3/HMPV-PreF-A vaccine, both designed to combat specific viruses that cause breathing problems in children. Participants will receive one of these vaccines or a placebo. Research has shown that these vaccines boost the immune system to better defend against HPIV3 and HMPV, which often lead to respiratory infections. Earlier studies with similar vaccines demonstrated that they can help protect against these infections by enhancing the body's natural defenses. Early results suggest these vaccines might provide more specific protection than general treatments. Although the data remains in the early stages, the vaccines have shown promise in preventing these viral infections in young children. ^{1 2 3 6 7}

Who Is on the Research Team?

Ruth Karron, M.D.

Principal Investigator

Center for Immunization Research, JHBSPH

Are You a Good Fit for This Trial?

This trial is for HPIV3-seropositive children aged 24 to less than 60 months who may have had breathing issues due to certain viruses. The study excludes those not meeting the age requirement or with conditions that could interfere with vaccine assessment.

Inclusion Criteria

Seropositive for HPIV3 antibody, defined as serum HPIV3 HAI titer >1:8

HAI Screening for HPIV3-neutralizing antibody is obtained within the calendar year of inoculation

I am up to date with all vaccinations recommended for my age.

Exclusion Criteria

Known hypersensitivity to any study product component

I am receiving treatment for a heart condition.

I have had wheezing or used a bronchodilator since turning 1 year old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Acute Phase

Participants receive a single dose of the study vaccine or placebo and are monitored daily for 28 days for adverse events and vaccine virus shedding

4 weeks

Daily contact, 9 in-person visits

Follow-up

Participants are monitored for Medically Attended Adverse Events (MAAEs) and Serious Adverse Events (SAEs) with monthly contacts and a final assessment on Day 180

22 weeks

Monthly contacts, 1 in-person visit on Day 180

What Are the Treatments Tested in This Trial?

Interventions

• B/HPIV3/HMPV-F-B365 vaccine
• B/HPIV3/HMPV-PreF-A vaccine

Trial Overview The trial tests two experimental nasal spray vaccines against respiratory viruses in young children. It aims to assess safety and how well these vaccines work, involving daily check-ins, physical exams, blood samples, and nasal swabs over six months.

How Is the Trial Designed?

Group I: B/HPIV3/HMPV-F-B365 vaccine Active Control 1 Intervention

A single dose of intranasal B/HPIV3/HMPV-F-B365 will be administered by a Vax300 VaxINator atomization device.

Group II: B/HPIV3/HMPV-PreF-A vaccine Active Control 1 Intervention

A single dose of intranasal B/HPIV3/HMPV-PreF-A will be administered by a Vax300 VaxINator atomization device.

Group III: Placebo Placebo Group 1 Intervention

A single dose of intranasal Lactated Ringer's Solution for Injection will be administered by a Vax300 VaxINator atomization device.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Johns Hopkins Bloomberg School of Public Health

Collaborator

Trials

441

Recruited

2,157,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

Published Research Related to This Trial

The updated immunization schedule now includes the acellular pertussis vaccine and hepatitis B vaccine for all infants, ensuring early protection against these diseases.

Children with specific health conditions, such as asthma, diabetes, or heart disease, are recommended to receive the influenza vaccine, highlighting the importance of targeted immunization for at-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Childhood immunization guidelines: current and future. Zimmerman, RK., Burns, IT.[2012]

The investigational hexavalent vaccine formulations were generally well tolerated in 60 healthy toddlers, with similar rates of injection-site reactions and fever compared to the licensed pentavalent vaccine.

Both new formulations of the hexavalent vaccine elicited comparable immune responses, although the PRP-T/HBV10 formulation showed higher anti-PRP antibody levels than the licensed vaccine, indicating potential for improved immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of two formulations of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae conjugate-hepatitis B vaccine in 15 to 18-month-old children. Halperin, SA., Langley, JM., Hesley, TM., et al.[2019]

Several Haemophilus influenzae type b vaccines, including PRP-D and HbOC, are licensed for children in the U.S., showing efficacy in preventing invasive disease.

However, there is a concerning increase in the incidence of invasive H influenzae type b disease shortly after vaccination, with studies indicating a 6.4 times greater rate of hospitalization for invasive disease within one week of immunization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease caused by Haemophilus influenzae type b in the immediate period after homologous immunization: immunologic investigation. Sood, SK., Daum, RS.[2012]

In a study of 64 healthy infants aged 2-3 months, those who received the PRP + P vaccine showed a significant immune response, with 70% achieving protective antibody levels against H. influenzae type b, compared to less than 10% for the PRP vaccine alone.

The DPT vaccine was associated with more frequent local and systemic reactions than the PRP vaccine, indicating that while DPT may be effective, it may also lead to more side effects in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a new Haemophilus influenzae type b vaccine in infants under one year of age. King, SD., Ramlal, A., Wynter, H., et al.[2019]

The new H influenzae type B conjugate vaccine, PedvaxHIB, effectively stimulates a strong immune response in infants as young as 2 months old, requiring only a single 15-microgram dose.

In a pilot study involving children aged 2 months to 4 years, the vaccine demonstrated consistent antibody responses and functional activity, indicating its potential for safe and effective immunization against H influenzae type B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opsonophagocidal activity in sera from infants and children immunized with Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate). Gray, BM.[2007]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06546423?cond=hmpv&amp;intr=VACCINE&amp;rank=5

Study of the Infectivity, Safety and Immunogenicity of Two ... The goal of this clinical trial is to look at the safety of 2 experimental HPIV3/HMPV vaccines in HPIV3-seropositive children ≥ 24 months to < 60 months of age.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12197412/

Vaccine Development for Human Pneumoviruses - PMC - B/HPIV3/HMPV-PreF-A - B/HPIV3/HMPV-F-B365 NIAID, Two recombinant LAVs B/HPIV3 vectors expressing fusion proteins of HMPV, Children 24 to <60 Months of Age ...

3. withpower.com withpower.com/trial/phase-1-human-parainfluenza-virus-type-3-6-2024-65fde

Vaccines for Respiratory Infections in Children The B/HPIV3/HMPV-F-B365 vaccine is unique because it targets specific respiratory viruses, potentially offering a more tailored approach compared to general ...

4. journals.lww.com journals.lww.com/ijsoncology/fulltext/9900/emerging_and_reemerging_human_metapneumovirus.31.aspx

Emerging and reemerging human metapneumovirus (hMPV) The majority of hMPV positive cases showed mild upper respiratory tract infections that resembled common cold, and recoup after a few days. ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12510674/

Landscape of Prophylactic Strategies Against Human ... Despite lower NAbs titers, these results suggested that rB/HPIV3‐HMPV F could protect against infections with both HMPV subtypes [70]. An ...

6. ctv.veeva.com ctv.veeva.com/study/study-of-the-infectivity-safety-and-immunogenicity-of-two-recombinant-live-attenuated-b-hpiv3-vec

Study of the Infectivity, Safety and Immunogenicity of Two ... The goal of this clinical trial is to look at the safety of 2 experimental HPIV3/HMPV vaccines in HPIV3-seropositive children ≥ 24 months to < ...

7. mdpi.com mdpi.com/2076-393X/13/6/569

Vaccine Development for Human Pneumoviruses These two LAVs, developed by NIAID, are intended to protect against HMPV and HPIV3, and recruitment for the phase 1 study is still ongoing [201].