The Role of Fatty Acids in Vaccine Efficacy

Study Overview
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Brief Summary
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This study intends to use a randomized controlled trial design to vaccinate all participants against rabies and perform ARA interventions during vaccination to test the efficacy, safety, and intestinal flora of each group after immunization.

Detailed Description
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Rabies is an acute zoonotic infectious disease caused by central nervous system invasion by rabies virus. At present, there is still a lack of effective treatment, and once clinical symptoms appear, it is almost 100% fatal. Rabies vaccination within 24 hours of exposure may reduce the incidence of rabies. Pre-exposure prophylaxis is also effective, and the current recommended pre-exposure vaccination program in China is 0 days, 7th day, 21st days. The health of the human body is inseparable from various nutrients. There are studies suggesting that arachidonic acid(ARA) has an immunomodulatory effect, but there is limited evidence for its effect on vaccines. Therefore, this study will explore the effects of nutritional supplements on the effectiveness of rabies vaccination.

Official Title
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The Role of Fatty Acids in Vaccine Efficacy: A Randomized Controlled Clinical Trial

Conditions
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Rabies Vaccination Reaction

Intervention / Treatment
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* Dietary Supplement: Arachidonic acid
* Dietary Supplement: Sunflower oil
* Biological: Rabies Vaccine (Vero Cell) for Human Use


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1）18-45 years old; 2）BMI 18.5-24.9 kg/m2; 3）Have not received rabies vaccination. Exclusion Criteria: 1) Those who have severe disorders of abnormal lipid metabolism; 2) Those who have used lipid-lowering drugs, weight loss drugs, and insulin drugs in the past three months; 3) Those who have received other vaccines in the past three months; 4) Those who have used probiotics or prebiotics in the past three months; 5) Those who have used steroids and immunosuppressants, other hormonal drugs in the past year; 6) Those with immunodeficiency diseases; 7) Those with a history of severe vaccine allergies; 8) Those who have disorders of liver and kidney metabolism; 9) Those who have had fever, cold, severe diarrhea and other diseases in the past month. 10) Smokers in the last year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>Sunflower oil capsules | Dietary Supplement: Sunflower oil<br>* The placebo group and D6 ARA group will receive sunflower oil capsules from the third day of the study. D6 ARA group will stop receiving sunflower oil capsules from the fifth day of the study.<br>Biological: Rabies Vaccine (Vero Cell) for Human Use<br>* Every participant will receive three doses of rabies vaccination.<br>|
| Experimental: D3 ARA group<br>ARA capsules | Dietary Supplement: Arachidonic acid<br>* D3 ARA group will receive ARA capsules from the third day of the study. D6 ARA group will receive ARA capsules from the sixth day of the study<br>Biological: Rabies Vaccine (Vero Cell) for Human Use<br>* Every participant will receive three doses of rabies vaccination.<br>|
| Experimental: D6 ARA group<br>Sunflower oil capsules and ARA capsules | Dietary Supplement: Arachidonic acid<br>* D3 ARA group will receive ARA capsules from the third day of the study. D6 ARA group will receive ARA capsules from the sixth day of the study<br>Dietary Supplement: Sunflower oil<br>* The placebo group and D6 ARA group will receive sunflower oil capsules from the third day of the study. D6 ARA group will stop receiving sunflower oil capsules from the fifth day of the study.<br>Biological: Rabies Vaccine (Vero Cell) for Human Use<br>* Every participant will receive three doses of rabies vaccination.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of rabies virus antibody titers | specific antibody titers | Day 6, 13, 16, 19, 26 of the study | 
| Changes of neutralizing antibody titers | To test the ability of binding to rabies virus | Day 6, 13, 16, 19, 26 of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum blood fatty acid profiles | to test the change of fatty acid profiles after intervention | Day 6, 13, 16，19 of the study | 
| C-reactive protein | to test the potential C-reactive protein changes triggered by ARA supplementation | Day 6, 13, 16 and 19 of the study | 
| Routine analysis of intestinal flora: alpha diversity | The alpha diversity of microbiota in feces samples will be examined to explore the potential gut-immune response caused by intervention. | Day 3 and day 19 of the study | 
| Routine analysis of intestinal flora: beta diversity | The beta diversity of microbiota in feces samples will be examined to explore the potential gut-immune response caused by the intervention. | Day 3 and day 19 of the study | 
| Routine analysis of intestinal flora: species abundance histogram | The species abundance histogram of microbiota in feces samples will be examined to explore the potential gut-immune response caused by the intervention. | Day 3 and day 19 of the study | 
| Routine analysis of intestinal flora: Lefse | The Lefse of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention. | Day 3 and day 19 of the study | 
| Routine analysis of intestinal flora: PLS-DA | The PLS-DA of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention. | Day 3 and day 19 of the study | 
| Routine analysis of intestinal flora: KEGG pathway | The KEGG pathway microbiota in feces samples will be analyzed to explore the potential gut-immune response caused by the intervention. | Day 3 and day 19 of the study | 
| Routine analysis of intestinal flora: differential KO expression | The differential KO expression microbiota in feces samples will be analyzed to explore the potential gut-immune response caused by the intervention. | Day 3 and day 19 of the study | 
| Macrogenomic sequencing difference of intestinal flora | The macrogenomic sequencing analysis of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention. | Day 3 and day 19 of the study | 
| Fecal fatty acid content | The fatty acid content in feces samples will be examined to explore the change of fatty acid intake caused by the intervention. | Day 3 and day 19 of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rabies Vaccination, Arachidonic acid, efficacy