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

22 Participants Needed

Trial Summary

What is the purpose of this trial?

Streptococcus pneumoniae, commonly called pneumococcus, can cause a wide range of diseases in children from mild ear infections to deadly pneumonia or meningitis. Vaccination is currently the single best way to protect children. Nutrition, especially the amount of vitamin A, may play a role in how well your body responds to infection or a vaccine. We call this an immune response. This research will look to see if children who take a vitamin with their vaccine have a better immune response than children who do not take a vitamin with their vaccine. Primary Objective To evaluate the influence of vitamin A supplementation on Prevnar vaccine immunogenicity based on changes in antibody scores in a commercial ELISA at Day 21 (after a booster vaccine dose) compared to pre-vaccine values. Secondary Objectives * To evaluate the relationship between baseline vitamin levels and pneumococcal or hepatitis A vaccine antibody responses (based on in commercial ELISAs) at Days 0 and 21. * To evaluate the influence of vitamin A supplementation on hepatitis vaccine immunogenicity based on changes in antibody scores in a commercial ELISA at Day 21 compared to pre-vaccine values. * To evaluate relationships between total serum antibodies (based on individual IgM, IgG1, IgG2, IgG3, IgG4, and IgA scores in a Luminex assay) at Day 0 and changes between Days 0 and 21 with baseline (Day 0) vitamin levels in young children, and with vitamin A supplementation.

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.

What data supports the effectiveness of the treatment Vitamin A for enhancing vaccine response?

Research shows that Vitamin A and its active form, retinoic acid, can boost the immune system by increasing antibody production, which is crucial for a strong vaccine response. However, some studies found no significant enhancement in vaccine response with Vitamin A supplementation, indicating mixed results. ^{1 2 3 4 5}

Is Vitamin A generally safe for humans?

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 in vitamin A-deficient individuals. However, the effects can vary based on baseline vitamin levels, and more research is needed for specific age groups like adults and the elderly. ^{1 6 7 8 9}

How does the drug Vitamin A differ from other treatments for enhancing vaccine response?

Vitamin A is unique because it enhances the immune response by increasing antibody production and improving the function of immune cells, which can lead to a stronger response to vaccines. Unlike other treatments, Vitamin A and its active form, retinoic acid, specifically modulate immune cell populations and cytokine production, potentially offering a novel way to boost vaccine efficacy. ^{1 2 3 10 11}

Research Team

Nehali Patel, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. United States 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. [2019]

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

Vitamin A, immunity, and infection. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Augmentation of antibody responses by retinoic acid and costimulatory molecules. [2018]

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

Neonatal vitamin A supplementation and immune responses to oral polio vaccine in Zimbabwean infants. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of Vitamin A supplementation on the immune response to measles vaccination. [2019]

6. Switzerland 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. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections in young children in Brazil. [2022]

8. United States 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. [2021]

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

Effects of vitamin a supplementation on immune responses and correlation with clinical outcomes. [2023]

10. United States 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. [2018]

11. England pubmed.ncbi.nlm.nih.gov

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