BCG-vaccination enhances immunogenicity of subsequent influenza vaccination in healthy volunteers: a randomized placebo-controlled double-blind pilot study


J Leentjens, M. Kox, R. Stokman, J. Gerretsen, D. Diavatopoulos, R. van Crevel, G. Rimmelzwaan, P. Pickkers, M. Netea

Voorzitter(s): prof. dr. R.P. Koopmans, MUMC, Maastricht & dr. C.J.A.M. Konings, Catharina Ziekenhuis, Eindhoven

Woensdag 22 april 2015

15:00 - 16:00u in Zaal 2.1

Categorieën: parallelsessie (case reports/research)

Parallel sessie: Parallelsessie 5: Case reports/research


Background:
Mortality due to influenza infection remains unacceptably high. Seasonal vaccination is the backbone of influenza management but often does not result in protective antibody titres. Non-specific effects of BCG-vaccination in humans have been reported, mediated by trained immunity and heterologous adaptive immune responses. As these effects increase the function of myeloid immune cells with antigen-presenting immunogenicity, we hypothesized that BCG vaccination could also enhance immune responses to other vaccines, including influenza vaccine.

Methods:
Healthy volunteers received BCG vaccine (n=20) or placebo (n=20) in a randomized double-blind fashion, followed by an intra-muscular injection of trivalent influenza vaccine 14 days later. Hemaglutination inhibiting (HI) antibodies and cellular immunity measured by cytokine production capacity were assessed 7, 14 and 28 days later.

Results:
In BCG-vaccinated subjects, HI antibody responses against the 2009 pandemic H1N1 vaccine strain were significantly enhanced compared with the placebo group, and seroconversion occurred more rapidly Statistical significant differences were not reached for the response to A/H3N2 and B vaccine strains. In addition, apart from more pronounced pro-inflammatory effects following BCG vaccination on ex-vivo leukocyte responses, nonspecific effects of influenza vaccination were also observed, with modulation of cytokine responses against unrelated pathogens.

Conclusion:
BCG vaccination prior to influenza vaccination results in a more pronounced increase and accelerated induction of functional antibody responses against the 2009 pandemic H1N1 influenza vaccine strain. These results may have implications for the design of vaccination strategies and could lead to improvement of influenza vaccination efficacy, which could have a major impact on public health.