Vitamin A for Vaccine Response Enhancement

Overseen By Nehali Patel, MD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Steroids, Antibiotics, Antivirals, others

Disqualifiers: Heart, Kidney, Respiratory, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether taking vitamin A with vaccines enhances the body's protection against infections like pneumonia and hepatitis in children. Researchers will compare children who receive vitamin A with their vaccines to those who do not, assessing their immune response at various intervals. Children between 1 and 4 years old, who have been off breast milk or formula for at least a month and have already received two doses of the Prevnar-13 vaccine, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination.

Will I have to stop taking my current medications?

The trial requires that participants do not use investigational or immunosuppressive drugs, antibiotics, antivirals, or daily vitamin A, vitamin D, or multivitamins during the study period. If your child is taking any of these, they would need to stop before joining the trial.

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

Research has shown that vitamin A supplements are usually safe. In studies where vitamin A was given with vaccines like diphtheria, children showed better immune responses, with increased antibodies, which help fight infections. However, some studies found higher risks with certain vaccine combinations, so these results require careful consideration.

Since this trial is in an early stage, researchers are still studying the treatment's safety. Previous research suggests vitamin A is generally safe, but more information is needed to confirm this when combined with the specific vaccines in this trial. Interested participants should discuss the possible risks and benefits with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Vitamin A to enhance vaccine responses because it offers a simple and natural way to potentially boost the effectiveness of vaccines like Prevnar-13 and Havrix. Unlike traditional vaccines that rely solely on the body's immune response, adding Vitamin A could amplify this response, leading to better protection against diseases. This approach is particularly appealing because Vitamin A is easily administered as a liquid supplement and is well-known for its immune-supporting properties. If successful, this could be a game-changer for improving vaccine efficacy with a readily available nutrient.

What evidence suggests that vitamin A supplementation might enhance vaccine response in children?

Research has shown that vitamin A can help the body fight infections by boosting the immune system. Some studies found that giving vitamin A to children with low vitamin levels can enhance their immune response to vaccines, potentially providing stronger protection after vaccination. In this trial, one group of participants will receive the PCV (Prevnar-13 Vaccine) and the hepatitis A vaccine (Havrix Vaccine) along with liquid oral vitamin A supplementation. Another group will receive the vaccines without vitamin A supplementation. While vitamin A has helped with some infections, it doesn't always work the same way for every vaccine. It remains safe and might be beneficial when used with certain vaccines. However, the effects of vitamin A can vary, so more research is needed to confirm these findings for the vaccines in this study. ^{6 7 8 9 10}

Who Is on the Research Team?

Nehali Patel, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for healthy children aged 1-4 who have been weaned off breast/formula feeding for at least 4 weeks and received at least two doses of Prevnar-13 vaccine. They can't join if they've had severe allergic reactions to certain vaccines, are on cancer treatments or immunosuppressive drugs, have a feverish illness close to enrollment, take daily vitamins during the study, or have chronic health conditions.

Inclusion Criteria

Parent or legal guardian willing and able to provide informed consent

Fully weaned from breast-feeding or formula-feeding for at least 4 weeks prior to vaccination date (Day 0)

I have received at least 2 doses of the Prevnar-13 vaccine.

Exclusion Criteria

I have a history of heart, kidney, or chronic respiratory issues like asthma.

I am currently undergoing treatment for cancer.

I plan to give my child daily vitamins during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Vaccination and Treatment

Participants receive PCV and hepatitis A vaccinations. The intervention group also receives vitamin A supplementation.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for antibody responses and vitamin levels at Day 21 post-vaccination.

3 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Vitamin A

Trial Overview The study tests whether vitamin A supplementation improves the immune response in young children receiving the Prevnar vaccine. It measures changes in antibody levels after taking vitamin A with their vaccine compared to those who don't supplement. The effect on hepatitis vaccine response is also studied.

How Is the Trial Designed?

Group I: Intervention group Experimental Treatment 1 Intervention

PCV (Prevnar-13 Vaccine) and the hepatitis A vaccine (Havrix Vaccine) plus a liquid oral vitamin A supplementation

Group II: Control group Experimental Treatment 1 Intervention

PCV (Prevnar-13 Vaccine) and the hepatitis A vaccine (Havrix Vaccine) only, 'No vitamin A supplementation'

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

The Gerber Foundation

Collaborator

Trials

45

Recruited

6,200+

Published Research Related to This Trial

In a study involving children aged 2 to 8 over three flu seasons, vitamin A and D supplementation significantly improved immune responses to the influenza vaccine in those with low baseline levels of these vitamins.

Conversely, children with sufficient levels of vitamins A and D at the start of the study showed weaker immune responses when supplemented, indicating that vitamin supplementation should be tailored based on individual vitamin status for optimal vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination. Patel, N., Penkert, RR., Jones, BG., et al.[2020]

Vitamin A supplementation in preschool children significantly reduces the risks of mortality and morbidity from diseases like diarrhea, measles, HIV, and malaria, primarily by enhancing immune function.

The benefits of vitamin A include improved antibody production and lymphocyte proliferation, which help in fighting infections, although its effects on adults and the elderly remain unclear and require further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of vitamin a supplementation on immune responses and correlation with clinical outcomes. Villamor, E., Fawzi, WW.[2023]

In a double-blind randomized study, administering Vitamin A to children with HIV before influenza vaccination did not improve their immune response to the vaccine.

However, Vitamin A did reduce the increase in HIV viral load 14 days post-immunization, suggesting a potential protective effect against viral replication during vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of vitamin A therapy on serologic responses and viral load changes after influenza vaccination in children infected with the human immunodeficiency virus. Hanekom, WA., Yogev, R., Heald, LM., et al.[2019]

In a study involving 1240 children aged 6-48 months in northeastern Brazil, periodic vitamin A supplementation significantly reduced the incidence of diarrhoea episodes compared to a placebo, with a notable 20% decrease in severe diarrhoea cases.

While vitamin A supplementation did not affect the incidence of acute lower-respiratory-tract infections (ALRI), the reduction in the severity of diarrhoea may contribute to lower childhood mortality rates associated with vitamin A supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections in young children in Brazil. Barreto, ML., Santos, LM., Assis, AM., et al.[2022]

Vitamin A plays a crucial role in enhancing immunity against infectious diseases, with clinical trials showing that supplementation significantly reduces severe illness and mortality in children with acute measles or in areas with vitamin A deficiency.

Vitamin A deficiency leads to various immune dysfunctions, but supplementation can improve immune responses by enhancing antibody production, increasing lymphocyte activity, and restoring mucosal surface integrity, suggesting its potential therapeutic use in infectious diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin A, immunity, and infection. Semba, RD.[2019]

In a randomized controlled trial involving 395 infants aged 9-12 months, Vitamin A supplementation did not enhance the immune response to the measles vaccine, as measured by antibody levels.

Interestingly, while not statistically significant, a lower proportion of infants who received Vitamin A had protective antibody levels six months after vaccination compared to those who did not receive the supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Vitamin A supplementation on the immune response to measles vaccination. Cherian, T., Varkki, S., Raghupathy, P., et al.[2019]

Intranasal vaccination in vitamin A-deficient mice did not produce normal levels of IgA, which is crucial for defending against respiratory viruses.

A single intranasal dose of retinyl palmitate alongside the vaccine successfully restored IgA responses, suggesting that vitamin A supplementation could enhance vaccine efficacy in populations lacking sufficient vitamin A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal administration of retinyl palmitate with a respiratory virus vaccine corrects impaired mucosal IgA response in the vitamin A-deficient host. Surman, SL., Jones, BG., Rudraraju, R., et al.[2021]

Vitamin A and its active form, all-trans-retinoic acid, can enhance antibody production in both vitamin A-deficient and adequate animals, which is important for effective vaccine responses.

The combination of retinoic acid with Toll-like receptor ligands boosts the adaptive immune response, improving both the initial antibody response and the recall response, likely by influencing B cell maturation and cytokine regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation of antibody responses by retinoic acid and costimulatory molecules. Ross, AC., Chen, Q., Ma, Y.[2018]

High-dose vitamin A supplementation during viral pneumonia did not improve recovery outcomes, such as disease severity or survival, in the study, which involved dietary interventions before and during infection.

While high vitamin A intake increased salivary IgA responses, it decreased the production of interferon-gamma (a Th1 cytokine), suggesting a shift towards a Th2-mediated immune response, which may not be beneficial for recovery from viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-level dietary vitamin A enhances T-helper type 2 cytokine production and secretory immunoglobulin A response to influenza A virus infection in BALB/c mice. Cui, D., Moldoveanu, Z., Stephensen, CB.[2018]

In a study of 181 infants in Zimbabwe, neonatal vitamin A supplementation (NVAS) did not significantly improve the immune response to oral polio vaccines, with only weak evidence of a difference for the Sabin-1 strain.

The results suggest that NVAS may not enhance vaccine efficacy in this population, indicating a need for further research on its effects on other oral vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neonatal vitamin A supplementation and immune responses to oral polio vaccine in Zimbabwean infants. Church, JA., Rukobo, S., Govha, M., et al.[2021]

Vitamin A and its related compounds are crucial for immune function, influencing various immune cells and processes, as shown in studies with animal models and cell lines.

Clinical trials indicate that vitamin A supplementation can significantly reduce illness and death rates from several infectious diseases, including measles and malaria, although its effects may vary depending on the specific infection and immune response involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin A and immunity to viral, bacterial and protozoan infections. Semba, RD.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6651517/

Influences of Vitamin A on Vaccine Immunogenicity and ... Here we provide a brief review of previous pre-clinical and clinical data, showing how VAD and VAS affect immune responses, vaccines, and infectious diseases.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0022316622092215

Vitamin A Supplementation Enhances Infants' Immune ... High-dose vitamin A supplementation has been shown to have no effect on the immunogenicity of oral polio vaccine, tetanus toxoid, pertussis, or on measles ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0002916523135386

Effect of high-dose vitamin A supplementation on the ... In conclusion, the results of the present study suggest that VAS does not influence the immunogenicity of BCG vaccination. If simultaneous VAS and BCG ...

4. withpower.com withpower.com/trial/phase-1-7-2019-1b546

Vitamin A for Vaccine Response Enhancement Vitamin A supplementation is generally considered safe for humans and has been shown to reduce the severity of diarrhea in children and improve immune responses ...

5. mdpi.com mdpi.com/1999-4915/11/10/907

Baseline Serum Vitamin A and D Levels Determine Benefit ... Overall, our study demonstrates that vitamin A&D supplementation can improve immune responses to vaccines when children are vitamin A and D-insufficient at ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7712358/

Multiple Vaccinations and the Enigma of Vaccine Injury - PMC For instance, children who received vitamin A with the diphtheria, tetanus, and pertussis (DTP) vaccine were at greater risk of death than ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31379816/

Influences of Vitamin A on Vaccine Immunogenicity and Efficacy Here we provide a brief review of previous pre-clinical and clinical data, showing how VAD and VAS affect immune responses, vaccines, and infectious diseases.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0022316623023441

Simultaneous Vitamin A Administration at Routine ... Our data demonstrate that vitamin A supplementation at routine immunization enhances the antibody response to diphtheria. Although the antibody responses to ...

9. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01576/full

Influences of Vitamin A on Vaccine Immunogenicity and ... Here we provide a brief review of previous pre-clinical and clinical data, showing how VAD and VAS affect immune responses, vaccines, and infectious diseases.

10. jn.nutrition.org jn.nutrition.org/article/S0022-3166(22)09221-5/pdf

Vitamin A Supplementation Enhances Infants' Immune ... High-dose vitamin A supplementation has been shown to have no effect on the immunogenicity of oral polio vaccine, tetanus toxoid, pertussis, or on measles ...