Effect of Oral Supplements for Influenza Vaccine Response

Официальное название

Effect of Oral Supplement Intervention on Influenza Vaccine Efficacy: a Randomized Controlled Clinical Trial

Обзор

The aim of this clinical trial is to explore the efficacy of fatty acid and bile acid based supplements on enhancing influenza vaccine immune response in adults aged 60-70 years. The objectives of this study are: 1. To explore the efficacy of fatty acid and bile acid based supplements on enhancing flu vaccine immune response. 2. To evaluate the safety of fatty acid and bile acid use in elders. 3. To explore the potential role of microbiota in regulating immune response. This study will conduct a randomized clinical trial to compare the efficacy of fatty acid / bile acid (Tauro Ursodesoxy Cholic Acid, TUDCA)supplements on enhancing vaccine immune response. The antibody's titer and safety indicators after influenza vaccination will be evaluated. Study process are: 1. Participants will be required to intake the assigned supplement or placebo daily for 25 days; 2. Receive a influenza vaccine on day 4; 3. Provide blood samples three times and stool samples twice at base line and endpoint respectively; 4. The antibody's titer and safety indicators will be analyzed and compared among groups. This study aims to establish a theoretical foundation for utilizing nutritional strategies to enhance vaccine-induced immune responses and to provide a scientific framework for developing oral vaccine boosters.

Подробное описание

Influenza virus infection presents a significant global health challenge, particularly threatening the elderly population due to immunosenescence. The immune response to influenza vaccination involves a complex series of events: after vaccination, hemagglutination inhibition antibody titers peak around day 14, accompanied by the production of neutralizing antibodies and other specific antibodies. This immune response gradually stabilizes to a post-response baseline level as immune memory establishes.

The age-related decline in immune function manifests through multiple mechanisms,including: reduced production of naive T cells; decreased diversity of T cell repertoire; compromised B cell function, altered cytokine production profiles which all diminished vaccine response efficacy.

Recent advances in immunometabolism have revealed the crucial role of specific fatty acids in immune system modulation. Our preliminary explorations found that，short-term Arachidonic Acid（AA）intervention could significantly reduce the time required for antibody production and enhance its levels following rabies vaccination. We also noticed that the serum Tauro Ursodesoxy Cholic Acid (TUDCA) was elevated in the intervention group. However, the related mechanism is still not clear.

The theoretical framework integrates nutritional immunology with classical vaccinology, focusing on the metabolic interaction between dietary fatty acids and immune cell function. This approach is particularly relevant for the elderly population, where reduced vaccine responsiveness due to immunosenescence presents a significant challenge in achieving optimal vaccine protection.

Вмешательства

• Пищевая добавка ARA (Arachidonic Acid) Supplementation
  Oral ARA (Arachidonic Acid) dietary supplement capsules, dosage 1000 mg/person/day. Capsule composition includes: C14:0 (0.15%), C16:0 (6.08%), C16:1 (0.15%), C18:0 (4.57%), C18:1 (19.65%), C18:2 (38.46%), C18:3 (0.87%), C20:0 (0.50%), C20:3 (2.00%), C20:4 (18.66%), C22:0 (1.81%), C24:0 (4.05%). Maintain original lifestyle during intervention, Day 0-Day 2 as adaptation period, receive quadrivalent influenza vaccine on Day 3, continue supplementation until Day 24.
• Препарат TUDCA (Tauroursodeoxycholic Acid) Supplementation
  Oral Double Wood brand TUDCA (Tauroursodeoxycholic Acid) dietary supplement capsules, dosage 1000 mg/person/day. Capsules primarily contain TUDCA, with 500 mg per serving (two capsules), other ingredients include gelatin and rice powder. Maintain original lifestyle during intervention, Day 0-Day 2 as adaptation period, receive quadrivalent influenza vaccine on Day 3, continue supplementation until Day 24.
• Пищевая добавка Placebo Supplementation
  Oral placebo capsules identical in appearance and smell, dosage 1000 mg/person/day. Placebo capsule composition includes: C14:0 (0.09%), C16:0 (6.12%), C16:1 (0.03%), C18:0 (3.50%), C18:1 (28.06%), C18:2 (59.40%), C20:0 (0.27%), C22:0 (0.76%), C24:0 (0.26%). Maintain original lifestyle during intervention, Day 0-Day 2 as adaptation period, receive quadrivalent influenza vaccine on Day 3, continue taking placebo until Day 24.
• Биопрепарат Shanghai Biological Quadrivalent Influenza Virus Inactivated Vaccine
  Administer Shanghai Biological Quadrivalent Influenza Virus Inactivated Vaccine, produced by Shanghai Biological Products Research Institute Co., Ltd. , specification 0.5ml/dose, containing 15.0 μg hemagglutinin (for each influenza virus strain), suitable for intramuscular injection in individuals 6 months and older. Administer one dose to all study participants on Day 3. Closely observe and record any potential adverse reactions after vaccination.

Первичные конечные точки

• Specific Antibody Levels and Neutralizing Antibody Responses to Influenza Vaccine [Срок оценки: Day 13 and Day 24]

Вторичные конечные точки (3)

• Changes in Inflammatory Markers [Срок оценки: Day 0 and Day 24]
• Gut Microbiota Composition Changes [Срок оценки: Day 0 and Day 24]
• Metabolomics Analysis [Срок оценки: Day 0, Day 13 and Day 24]

Критерии участия

Критерии включения

• Age 60-70 years old
• Body Mass Index (BMI) 18.5-26.9 kg/m²
• No influenza vaccination in the past year
• Able to understand and sign the informed consent form, and capable of completing the full follow-up process

Критерии исключения

• Severe lipid metabolism disorders
• Use of lipid-lowering medications, weight loss drugs, or insulin within the past three months
• Vaccination with other vaccines within the past three months
• Use of probiotics or prebiotics within the past three months
• Use of steroids, immunosuppressants, or other hormonal medications within the past year
• Immunodeficiency diseases
• Severe vaccine allergy history
• Liver or kidney metabolic disorders
• Occurrence of fever, common cold, severe diarrhea, or other diseases within the past month
• Poorly controlled chronic diseases (such as blood pressure, blood sugar)
• Intake of influenza antiviral drugs within the past two weeks
• Cognitive function impairment
• Planning to undergo surgery in the near future

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Tsinghua University — Пекин

Публикации

• Sainz T, Casas I, Gonzalez-Esguevillas M, Escosa-Garcia L, Munoz-Fernandez MA, Prieto L, Gosalbes MJ, Jimenez-Hernandez N, Ramos JT, Navarro ML, Mellado MJ, Serrano-Villar S, Calvo C. Nutritional Supplementation to Increase Influenza Vaccine Response in Children Living With HIV: A Pilot Clinical Trial. Front Pediatr. 2022 Jul 19;10:919753. doi: 10.3389/fped.2022.919753. eCollection 2022. PMID 35928688
• D'Onofrio V, Porrez S, Jacobs B, Alhatemi A, De Boever F, Waerlop G, Michels E, Vanni F, Manenti A, Leroux-Roels G, Platenburg PP, Hilgers L, Leroux-Roels I. Safety and Immunogenicity of a Carbohydrate Fatty Acid Monosulphate Ester Adjuvant Combined with a Low-Dose Quadrivalent Split-Virion Inactivated Influenza Vaccine: A Randomised, Observer-Blind, Active-Controlled, First-in-Human, Phase 1 Stud PMID 39340066
• Chou CH, Mohanty S, Kang HA, Kong L, Avila-Pacheco J, Joshi SR, Ueda I, Devine L, Raddassi K, Pierce K, Jeanfavre S, Bullock K, Meng H, Clish C, Santori FR, Shaw AC, Xavier RJ. Metabolomic and transcriptomic signatures of influenza vaccine response in healthy young and older adults. Aging Cell. 2022 Sep;21(9):e13682. doi: 10.1111/acel.13682. Epub 2022 Aug 23. PMID 35996998

Идентификаторы

NCT: NCT06827873 · THU01-20240201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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