RSV Vaccine for Respiratory Syncytial Virus

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and immune response of a new vaccine for the respiratory syncytial virus (RSV), a common cause of lung infections in young children. The study includes healthy children who have either had RSV or not, and healthy infants not checked for previous RSV infections. Participants will receive either the experimental RSV ΔNS2 Δ1313 I1314L Vaccine or a placebo, both administered as nose drops. Ideal participants are healthy children or infants who have experienced RSV or haven't been exposed to it and do not have lung or heart problems. As a Phase 1 trial, this research focuses on understanding how the new vaccine works in people, offering participants the chance to be among the first to receive this innovative treatment.

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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the RSV ΔNS2 Δ1313 I1314L vaccine has been tested for safety in people. In an earlier study, 64% of those who received the vaccine experienced mild cold-like symptoms, such as a runny nose or mild fever, within 28 days. In comparison, 58% of those who received a placebo, a harmless substance with no active ingredients, also experienced these symptoms. This indicates that such symptoms are common even without the vaccine. Notably, these symptoms were usually mild and resolved on their own. This suggests that the vaccine is generally safe, with side effects similar to a common cold. The study involved infants and toddlers, similar to the group in the current trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional RSV vaccines that primarily focus on protein-based formulations, the RSV ΔNS2 Δ1313 I1314L vaccine is a live-attenuated vaccine. This means it uses a weakened form of the virus, aiming to provoke a strong immune response without causing the disease. Researchers are excited because this vaccine is administered as nose drops, directly targeting the respiratory tract where RSV infections occur. This delivery method could potentially enhance the body's natural defense at the initial site of infection, possibly leading to more effective prevention of RSV in young children.

What evidence suggests that this RSV vaccine could be effective for respiratory syncytial virus?

Research has shown that the RSV ΔNS2 Δ1313 I1314L vaccine, which participants in this trial may receive, holds promise for treating respiratory syncytial virus (RSV). In earlier studies, this vaccine led to fewer cases of upper respiratory illness and fever compared to other RSV vaccines. Specifically, 64% of recipients experienced mild respiratory symptoms, compared to 84% in another vaccine group. Designed to be less harmful, this vaccine has demonstrated moderate sensitivity to temperature changes, potentially making it safer and more stable. Overall, these early findings suggest that this vaccine could protect against RSV with fewer side effects. ^{2 4 6 7 8}

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

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]

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 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35732186/

Evaluation of Recombinant Live-Attenuated Respiratory ... During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10205613/

Evaluation of Recombinant Live-Attenuated Respiratory ... During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03916185

Study Details | NCT03916185 | Safety and Immunogenicity ... This study evaluated the safety and immunogenicity of a single dose of the recombinant live-attenuated respiratory syncytial virus (RSV) vaccines, RSV ΔNS2/Δ ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2445146024000190

Current situation of intranasal attenuated vaccines against ... The combination of the Δ1313 deletion with the NS2 deletion was shown to be better for the development of an attenuated RSV recombinant vaccine candidate (ΔNS2/ ...

5. mdpi.com mdpi.com/2076-393X/13/3/304

Progress on Respiratory Syncytial Virus Vaccine ... The most advanced NS2-deficient live attenuated RSV vaccine is RSV/ΔNS2/Δ1313/I1314L, which exhibits low toxicity and moderate temperature sensitivity [37]. A ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31605113/

Safety and Immunogenicity of the Respiratory Syncytial Virus ... RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the ...

7. evidence.nejm.org evidence.nejm.org/doi/abs/10.1056/EVIDoa2500026

Live-Attenuated Intranasal RSV Vaccine in Infants and Toddlers RSV/ΔNS2/Δ1313/I1314L (RSVt) (Sanofi) is a candidate live-attenuated intranasal respiratory syncytial virus (RSV) vaccine for infants and toddlers.

8. pure.johnshopkins.edu pure.johnshopkins.edu/en/publications/safety-and-immunogenicity-of-the-respiratory-syncytial-virus-vacc

Safety and immunogenicity of the respiratory syncytial virus ... RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the ...