Outcomes of controlled human malaria infection after BCG vaccination

Abstract

Recent evidence suggests that certain vaccines, including Bacillus-Calmette Guérin (BCG), can induce changes in the innate immune system with non-specific memory characteristics, termed ‘trained immunity’. Here we present the results of a randomised, controlled phase 1 clinical trial in 20 healthy male and female volunteers to evaluate the induction of immunity and protective efficacy of the anti-tuberculosis BCG vaccine against a controlled human malaria infection. After malaria challenge infection, BCG vaccinated volunteers present with earlier and more severe clinical adverse events, and have significantly earlier expression of NK cell activation markers and a trend towards earlier phenotypic monocyte activation. Furthermore, parasitemia in BCG vaccinated volunteers is inversely correlated with increased phenotypic NK cell and monocyte activation. The combined data demonstrate that BCG vaccination alters the clinical and immunological response to malaria, and form an impetus to further explore its potential in strategies for clinical malaria vaccine development.

Emerging role of γδ T cells in vaccine‐mediated protection from infectious diseases

“…59,60 Furthermore, these cells can also act as antigenpresenting cells, [61][62][63][64] which may further enhance the response to infection and/or vaccination. 66 Trends towards increased degranulation and granzyme B production among cd T cells from BCG-vaccinated volunteers compared to unvaccinated were also observed. 65 Elevated frequencies of cd T cells expressing effector memory surface markers and enhanced responsiveness to Pf stimulation persist for over 1 year following experimental infectious challenge.…”

“…Interestingly, expression of the activation marker CD69 on both NK cells and cd T cells was associated with reduced parasitaemia. 66 Trends towards increased degranulation and granzyme B production among cd T cells from BCG-vaccinated volunteers compared to unvaccinated were also observed. 66 Together, these results suggest an important role for cd T cells in mediating protective immunity to malaria.…”

“…In malaria-na€ ıve volunteers exposed to Pf-infected mosquitoes, while under chloroquine prophylaxis, cd T cells expand after infection. 66 Together, these results suggest an important role for cd T cells in mediating protective immunity to malaria. 65 A recent small study from the same group reported that vaccination with BCG changed the course of experimental malaria infection and that BCG vaccination was associated with altered innate immune activation (including cd, NK and monocytes) following malaria challenge.…”

“…BCG vaccination may be a potential approach based on recent results of increased activation of innate cell populations following CHMI in BCGvaccinated individuals; 66 however, given that this response only occurred in half of the vaccinated volunteers and the sample size was small, further study is warranted. However, future work is required to definitively show that cd T cells directly mediate protection rather than act as a biomarker of infection, as well as to determine the mechanism of protection and the role of Vd2 À subsets (if any).…”

“…Given that most malaria vaccines in trials, including the leading RTS,S vaccine, use specific antigens rather than whole sporozoites, vaccine effectiveness may be improved by the addition of an adjuvant or other vaccine component that stimulates cd T-cell responses. BCG vaccination may be a potential approach based on recent results of increased activation of innate cell populations following CHMI in BCGvaccinated individuals; 66 however, given that this response only occurred in half of the vaccinated volunteers and the sample size was small, further study is warranted.…”