Lack of homologous protection against Campylobacter jejuni CG8421 in a human challenge model

Abstract

Background: Campylobacter jejuni is a common cause of diarrhea and is associated with serious postinfectious sequelae. Although symptomatic and asymptomatic infections are recognized, protective immunity is not well understood. Previous data suggests that interferon γ (IFN-γ) may be associated with protection. To better define the clinical and immunologic development of protective immunity to C. jejuni, we assessed the ability of an initial infection to prevent clinical illness after a second experimental infection.

Methods: Subjects with no clinical or immunologic evidence of prior infection with C. jejuni received an initial challenge with C. jejuni CG8421 with rechallenge 3 months later. The primary endpoint was campylobacteriosis, as defined by diarrhea and/or systemic signs. Close inpatient monitoring was performed. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG), fecal IgA, IgA antibody-secreting cells (ASCs), and IFN-γ production were evaluated. All subjects were treated with antibiotics and were clinically well at discharge.

Results: Fifteen subjects underwent a primary infection with C. jejuni CG8421; 14 (93.3%) experienced campylobacteriosis. Eight subjects received the second challenge, and all experienced campylobacteriosis with similar severity. Immune responses after primary infection included serum IgA, IgG, ASC, and IFN-γ production. Responses were less robust after secondary infection.

Conclusions: In naive healthy adults, a single infection with CG8421 did not protect against campylobacteriosis. Although protection has been demonstrated with other strains and after continuous environmental exposure, our work highlights the importance of prior immunity, repeated exposures, and strain differences in protective immunity to C. jejuni.

Clinical trials registration: NCT01048112.

Keywords: Campylobacter jejuni; Campylobacterosis; homologous protection; human challenge model.

Figures

Figure 1.

Screening eligibility and enrollment of volunteers participating in the Campylobacter jejuni challenge and rechallenge trial. Abbreviations: IFN-γ, interferon γ; IgA, immunoglobulin A.

Figure 2.

Serum immunoglobulin G (IgG), immunoglobulin A (IgA), and fecal IgA responses after challenge (day 0) and secondary challenge (day 98) with Campylobacter jejuni CG8421. A, Serum IgG responses after primary (day 0) and secondary (day 98) challenge with C. jejuni CG8421. B, Serum IgA responses after primary (day 0) and secondary (day 98) challenge with C. jejuni CG8421. C, Fecal IgA responses after primary (day 0) and secondary (day 98) challenge with C. jejuni CG8421. Hatched lines represent total fecal IgA. Solid lines represent C. jejuni antigem-specific fecal IgA. Abbreviation: IgA, immunoglobulin A.

Figure 3.

Immunoglobulin A antibody-secreting cell responses after primary and secondary challenge with Campylobacter jejuni CG8421. Horizontal lines denote the median number of antibody-secreting cells for each day. Abbreviations: ASC, antibody-secreting cell; IgA, immunoglobulin A; PBMC, peripheral blood mononuclear cell.

Figure 4.

Interferon γ produced from peripheral blood mononuclear cells after primary and secondary challenge. Horizontal lines denote median interferon γ levels for each study day. Abbreviations: IFN-γ, interferon γ; PBMC, peripheral blood mononuclear cell.