A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials

doi:10.1016/j.vaccine.2009.06.094

Vaccine

Volume 27, Issue 41, 18 September 2009, Pages 5677-5684

https://doi.org/10.1016/j.vaccine.2009.06.094 Get rights and content

Abstract

Background

Influenza vaccination is recommended for the elderly in many countries, but immune responses are weaker compared to younger adults.

Objective

To investigate the impact of daily consumption of a probiotic dairy drink on the immune response to influenza vaccination in an elderly population of healthy volunteers over 70 years of age.

Design

Two randomised, multicentre, double-blind, controlled studies were conducted during two vaccination seasons in 2005–2006 (pilot) and 2006–2007 (confirmatory). Eighty-six and 222 elderly volunteers consumed either a fermented dairy drink, containing the probiotic strain Lactobacillus casei DN-114 001 and yoghurt ferments (Actimel^®), or a non-fermented control dairy product twice daily for a period of 7 weeks (pilot) or 13 weeks (confirmatory). Vaccination occurred after 4 weeks of product consumption. Geometric mean antibody titres (GMT) against the 3 viral strains composing the vaccine (H1N1, H3N2, and B) were measured at several time intervals post-vaccination by haemagglutination inhibition test.

Results

In the pilot study, the influenza-specific antibody titres increased after vaccination, being consistently higher in the probiotic product group compared to the control group under product consumption. Similarly, in the confirmatory study, titres against the B strain increased significantly more in the probiotic group than in the control group at 3, 6 and 9 weeks post-vaccination under product consumption (p = 0.020). Significant differences in seroconversion between the groups by intended to treat analysis were still found 5 months after vaccination. Similar GMT results were observed for the H3N2 strain and H1N1 strain, confirming the results of the pilot study.

Conclusion

These studies demonstrate that daily consumption of this particular probiotic product increased relevant specific antibody responses to influenza vaccination in individuals of over 70 years of age and may therefore provide a health benefit in this population.

Introduction

Influenza viruses are a major cause of respiratory infection worldwide. The World Health Organisation (WHO) estimates that, in annual influenza epidemics, between 5% and 15% of the population are affected by upper respiratory tract infection. The elderly are particularly at risk of influenza, especially infection with complications that result in severe illness requiring hospitalisation or death [1]. Between 250,000 and 500,000 deaths worldwide are attributable each year to influenza, with most of these deaths occurring in individuals over 65 years of age.

Influenza vaccination is the primary preventive measure against infection and reduces the severity and duration of the infection and associated complications [2], [3]. In young healthy adults, the influenza vaccine provides a protective clinical efficacy in 70–90% of cases, which is reduced to only 17–53% in elderly individuals [4]. Such reduced efficacy is thought to be due to the age-related decline in the function of the immune system, a physiological phenomenon named immunosenescence [5]. Indeed, following influenza vaccination, seroconversion and seroprotection rates are two- to fourfold lower in the elderly compared to younger individuals [4]. Thus simple strategies to improve the immune response to influenza vaccine in the elderly would be of major public health benefit.

The addition of an adjuvant such as MF59 to the vaccine has been associated with enhanced immunogenicity and subsequent improved protection against influenza [5], [6]. An alternative method to improve the response to the vaccine could be the consumption of probiotics in foods or drinks, as part of the normal diet. Probiotics are defined as live micro-organisms that, when administered in adequate amount, confer a health benefit to the host [7]. Oral administration of specific probiotics has been reported to enhance innate and adaptive immunity in the host [7], [8], such as response to polio vaccine [9].

Actimel^® is a fermented dairy drink containing the probiotic organism Lactobacillus casei DN-114 001 [10] and regular yoghurt ferments. In vitro studies, in vivo studies in animals, and clinical trials showed that this probiotic product can enhance immune responses at the systemic level [11], [12], [13], [14], [15] and have a positive impact on the health of elderly subjects [15], [16].

The aim of the clinical studies reported here was to investigate the effect of regular consumption of the probiotic drink Actimel^® on the specific antibody responses to influenza vaccination in healthy elderly subjects.

Section snippets

Overall organization of clinical studies

Two randomised, controlled, double-blind, multicentre clinical trials were conducted in France in elderly volunteers during the vaccination seasons of 2005–2006 and 2006–2007. The earlier trial was a pilot study conducted in 10 nursing homes. The confirmatory clinical study was conducted, with more subjects, in 31 nursing homes.

The pilot protocol and informed consent form were approved by the Independent Ethics Committee (IEC)/Institutional Review Board (IRB) of Nancy, France, on 12 July 2005.

Pilot study: positive tendencies on antibody responses for the probiotic product group

In the pilot study, 136 healthy elderly individuals were screened with 86 finally included and randomised to the 2 study groups. Forty-four subjects were allocated to the probiotic group and 42 to the control group. There were no differences between the two groups in terms of baseline demographics, medical history or current disease (Table 2). Eleven subjects prematurely discontinued the study: 9 withdrew because of an adverse event – only 2 in the probiotic group vs. 7 in the control group –

Discussion

In these studies, we show that consumption of a commercially available probiotic drink, in a study group of people over 70 years, helps in raising specific antibody titres after vaccination against influenza.

Seasonal influenza epidemics are a major public health concern, especially for the elderly in whom complications upon influenza virus infection may occur. Moreover, it is known that the elderly respond poorly to vaccination compared to younger adults as a result of the decline in immune

Acknowledgements

Dr. Sandrine Samson (Danone Research) for development of study concepts and designs, analysis and interpretation of the data. Pr. Claude Leclerc (Pasteur Institute, Paris), Pr. Thomas MacDonald (Queen Mary Institute, London) and Pr. Eric Claassen (Erasmus Medical Centre & Viroventures, Rotterdam) for thoughtful discussions on these studies and help in the writing of the publication. Dr. Jean-Thierry Aubin and members of the National Influenza Centre (Northern France) (Pasteur Institute, Paris)

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^☆: The study was sponsored by Danone Research, France. After design of the study, all research was conducted independently without influence from the sponsor.

View full text

A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials☆

Abstract

Background

Objective

Design

Results

Conclusion

Introduction

Section snippets

Overall organization of clinical studies

Pilot study: positive tendencies on antibody responses for the probiotic product group

Discussion

Acknowledgements

Vaccine

Vaccine

Vaccine

Ann Readapt Med Phys

Vaccine

Nutrition

Vaccine

Influenza in elderly people in care homes

BMJ

Effectiveness of influenza vaccine in the community-dwelling elderly

N Engl J Med

Age-related changes in immunity: implications for vaccination in the elderly

Expert Rev Mol Med

Probiotics, immunomodulation, and health benefits

Adv Exp Med Biol

Immunomodulatory effects of probiotics in different stages of life

Br J Nutr

Probiotic bacteria stimulate virus-specific neutralizing antibodies following a booster polio vaccination

Eur J Nutr

Multilocus sequence typing of Lactobacillus casei reveals a clonal population structure with low levels of homologous recombination

Appl Environ Microbiol

The effect of milk fermented by yogurt cultures plus Lactobacillus casei DN-114001 on the immune response of subjects under academic examination stress

Eur J Nutr