RSV Vaccine for Respiratory Syncytial Virus

Recruiting at 1 trial location

Overseen By Jocelyn San Mateo

Age: < 18

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Immunosuppressants, Systemic corticosteroids

Disqualifiers: Immunological impairment, Congenital malformations, Lung or heart disease, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new RSV vaccine given as nose drops to help protect against lung infections caused by the RSV virus. It involves healthy children and infants, including those who have and have not had an RSV infection before. The vaccine works by teaching the body to recognize and fight the virus.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like systemic steroids or recent vaccines may affect eligibility, so it's best to discuss your specific situation with the study team.

Is the RSV ΔNS2 Δ1313 I1314L Vaccine safe for humans?

The RSV ΔNS2 Δ1313 I1314L Vaccine has been tested for safety in children who have not been exposed to RSV before, and it was found to be safe and well-tolerated in these studies. ^{1 2 3 4 5}

How is the RSV ΔNS2 Δ1313 I1314L vaccine different from other RSV treatments?

The RSV ΔNS2 Δ1313 I1314L vaccine is unique because it is a live vaccine that has been genetically modified to be less harmful by deleting certain genes, making it temperature-sensitive and stable. This approach is different from current prevention methods, which rely on hygiene and expensive antibodies for high-risk children. ^{1 2 6 7 8}

What data supports the effectiveness of the RSV ΔNS2 Δ1313 I1314L Vaccine treatment for Respiratory Syncytial Virus?

The research highlights promising vaccine candidates for RSV, including those with similar genetic modifications like the deletion of the NS2 gene, which have shown potential in inducing protective immunity in children. This suggests that the RSV ΔNS2 Δ1313 I1314L Vaccine may also be effective in preventing RSV-related illnesses. ^{1 4 6 9 10}

Who Is on the Research Team?

Ruth A. Karron, MD

Principal Investigator

Johns Hopkins Bloomberg School of Public Health

Are You a Good Fit for This Trial?

This trial is for healthy infants and children aged 12 to 59 months. It includes those who have had RSV before (seropositive) and those who haven't (seronegative), as well as younger infants not screened for RSV. Participants must be in good health, available for the study duration, and have parental consent.

Inclusion Criteria

Seropositive for RSV as defined by serum RSV neutralizing antibody titer equal to or greater than 1:40

Participant's history has been reviewed and participant has undergone a physical examination indicating that s/he is in good health

Seronegative for RSV antibody, defined as a serum RSV neutralizing antibody titer less than 1:40 as determined not more than 42 days prior to inoculation

Exclusion Criteria

Known hypersensitivity to any vaccine component

Previous serious vaccine-associated AE or anaphylactic reaction

Attends day care with infants less than 6 months of age, and whose parent/guardian is unable or unwilling to suspend daycare for 14 days following immunization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of the RSV vaccine or placebo administered as nose drops

1 day

1 visit (in-person)

Initial Follow-up

Participants are actively monitored for safety and immune response, including medical history reviews, clinical assessments, and nasal washes

28 days for Group 1, 56 days for Groups 2, 3, and 4

Multiple visits (in-person), regular contact (telephone)

Extended Follow-up

Parents or guardians monitor participants for RSV-associated illnesses and report weekly; additional study visits may occur

November through March following vaccination

Long-term Follow-up

Participants in Groups 3 and 4 have the option for additional monitoring for a second RSV season

Up to 1 year after study entry

What Are the Treatments Tested in This Trial?

Interventions

• RSV ΔNS2 Δ1313 I1314L Vaccine

Trial Overview The trial tests a new vaccine called RSV ΔNS2 Δ1313 I1314L against a placebo to see if it's safe and how well it triggers an immune response in kids with different histories of RSV infection.

How Is the Trial Designed?

Group I: Group 4: RSV vaccine Experimental Treatment 1 Intervention

Healthy infants between the ages 4 to 6 months who have not been screened for RSV serostatus will receive one dose of the RSV ΔNS2 Δ1313 I1314L vaccine administered as nose drops at study entry.

Group II: Group 3: RSV vaccine Experimental Treatment 1 Intervention

Healthy RSV-seronegative infants and children ages 6 to 24 months will receive one dose of the RSV ΔNS2 Δ1313 I1314L vaccine administered as nose drops at study entry.

Group III: Group 2: RSV vaccine Experimental Treatment 1 Intervention

Healthy RSV-seronegative infants and children ages 6 to 24 months will receive one dose of the RSV ΔNS2 Δ1313 I1314L vaccine administered as nose drops at study entry.

Group IV: Group 1: RSV vaccine Experimental Treatment 1 Intervention

Healthy RSV-seropositive children ages 12 to 59 months will receive one dose of the RSV ΔNS2 Δ1313 I1314L vaccine administered as nose drops at study entry.

Group V: Group 4: Placebo Placebo Group 1 Intervention

Healthy infants between the ages 4 to 6 months who have not been screened for RSV serostatus will receive one dose of the placebo administered as nose drops at study entry.

Group VI: Group 2: Placebo Placebo Group 1 Intervention

Healthy RSV-seronegative infants and children ages 6 to 24 months will receive one dose of the placebo administered as nose drops at study entry.

Group VII: Group 3: Placebo Placebo Group 1 Intervention

Healthy RSV-seronegative infants and children ages 6 to 24 months will receive one dose of the placebo administered as nose drops at study entry.

Group VIII: Group 1: Placebo Placebo Group 1 Intervention

Healthy RSV-seropositive children ages 12 to 59 months will receive one dose of the placebo administered as nose drops at study entry.

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+

Published Research Related to This Trial

Respiratory syncytial virus (RSV) poses a significant health risk not only to infants but also to older adults, prompting urgent vaccine development efforts, with 19 candidates currently in clinical trials.

Advancements in understanding the RSV surface fusion glycoprotein have led to innovative vaccine strategies, including particle-based, live-attenuated, subunit, and vector-based approaches, although past trial failures indicate the need for improved knowledge on immunological protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. Mazur, NI., Higgins, D., Nunes, MC., et al.[2023]

The Gcf A/Bac M2 vaccine candidate successfully induced strong Th1 and CD8+ T-cell responses in mice, leading to effective protective immunity against respiratory syncytial virus (RSV) without causing vaccine-enhanced disease (VED).

This vaccine formulation also resulted in a significant increase in IgG responses compared to Gcf A alone, suggesting that Bac M2 acts as an effective adjuvant, enhancing the immune response to RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus. Jo, YM., Kim, J., Chang, J.[2022]

The Ad26.RSV.preF vaccine candidate showed good safety and immunogenicity in a study involving 12 adults and 36 RSV-seropositive children, with no serious adverse events reported and only mild to moderate reactions observed.

The vaccine significantly increased RSV neutralization titers in children and resulted in fewer RSV infections compared to the placebo group, indicating its potential effectiveness in preventing RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months. Stuart, ASV., Virta, M., Williams, K., et al.[2023]

The investigational ChAd155-RSV vaccine was found to have a safety profile similar to other childhood vaccines, with most adverse events occurring at rates comparable to or lower than those of active comparators.

The vaccine induced a strong immune response in infants, with higher RSV neutralizing titers and antibody concentrations compared to the comparator group, and there was no evidence of vaccine-associated enhanced respiratory disease (VAERD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a ChAd155-vectored respiratory syncytial virus vaccine in infants 6-7 months of age: a phase 1/2 randomized trial. Sáez-Llorens, X., Norero, X., Mussi-Pinhata, MM., et al.[2023]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the live-attenuated intranasal respiratory syncytial virus (RSV) vaccine RSV/6120/ΔNS2/1030s in RSV-seronegative young children. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: a phase 1, randomised, open-label, dose-escalation clinical trial. [2022]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a ChAd155-vectored respiratory syncytial virus vaccine in infants 6-7 months of age: a phase 1/2 randomized trial. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Current State and Challenges in Developing Respiratory Syncytial Virus Vaccines. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Live-Attenuated Respiratory Syncytial Virus Vaccine With M2-2 Deletion and With Small Hydrophobic Noncoding Region Is Highly Immunogenic in Children. [2021]