Immunization with SsEno fails to protect mice against challenge withStreptococcus suisserotype 2

Abstract

In our ongoing efforts to develop a vaccine against Streptococcus suis infection, we tested the potential of S. suis enolase (SsEno), a recently described S. suis adhesin with fibronectin-binding activity, as a vaccine candidate in a mouse model of S. suis-induced septicemia and meningitis. Here, we show that SsEno is highly recognized by sera from convalescent pigs and is highly immunogenic in mice. Subcutaneous immunization of mice with SsEno elicited strong immunoglobulin G (IgG) antibody responses. All four IgG subclasses were induced, with IgG1, IgG2a and IgG2b representing the highest titers followed by IgG3. However, SsEno-vaccinated and nonvaccinated control groups showed similar mortality rates after challenge infection with the highly virulent S. suis strain 166'. Similar results were obtained upon passive immunization of mice with hyperimmunized rabbit IgG anti-SsEno. We also showed that anti-SsEno antibodies did not increase the ability of mouse phagocytes to kill S. suis in vitro. In conclusion, these data demonstrate that although recombinant SsEno formulated with Quil A triggers a strong antibody response, it does not confer effective protection against infection with S. suis serotype 2 in mice.

Streptococcus suisinfection

“…Among them, eight enzymes are proposed to be virulence factors by Wilson et al 100 using the system of signature-tagged mutagenesis (Table 2). Four of them are generally regarded as enzymes of central metabolism, which separately correspond to (1) GlnA, glutamine synthetase, 127 (2) Gdh, glutamate dehydrogenase, 128 (3) enolase catalyzing dehydration of 2-phosphoglycerate to phosphor-enolpyruvate, 96 , 129 , 130 and (4) Impdh, inosine 5-monophosphate dehydrogenase 131 . Five of these enzymes are directly or indirectly related to synthesis and/or modification of bacterial surface structure, including DltA, an enzyme catalyzing lipoteichoic d -alanylation, 132 PgdA, peptidoglycan N-acetylglucosamine deacetylase, 133 ApuA, a bifunctional amylopullulanase, 134 DPP IV, di-peptidyl peptidase IV, 135 and sortase A, a transpeptidase 136 , 137 .…”

“…We and two other research groups 96 , 129 , 143 have reported that S. suis enolase acts as an octamer, 144 and can exported to the bacterial surface with capability of binding to host fibronectin, indicating its possible role in crosstalk between pathogen and host. However, the protective efficiency of recombinant enolase with different bacterial origins does not seem consistent 96 , 129 , 130 . Similarly, the gene encoding Inosine 5-monophosphate dehydrogenase, a nucleotide metabolism-related enzyme, was initially cloned by Lu’s research group, and was subsequently suggested to be involved in full virulence of SS2-H, a Chinese strain in the infection model of piglets 131 …”

“…Two different research groups from China confirmed that enolase, an enzyme of central metabolism, acts as a protective antigen displayed on bacterial surface 96 , 129 . However, Esgleas and coworker 130 reported an opposite result regarding the protective efficiency of enolase in mice. This discrepancy could be due to different versions of recombinant protein, different strains plus deviations in animal vaccination protocols.…”

Porcine Dendritic Cells as an In Vitro Model to Assess the Immunological Behaviour of Streptococcus suis Subunit Vaccine Formulations and the Polarizing Effect of Adjuvants

“…Furthermore, enolase is a highly conserved protein, and anti-enolase antibodies have been detected in convalescent pig sera [11]. Nevertheless, immunization studies showed that protection conferred by enolase seems to depend on the adjuvant used in the vaccine formulation [12,13,14]. Similarly, it was recently reported that generation of protective antibodies after immunization with S. suis CPS as antigen was restricted to CPS conjugation to an immunogenic carrier protein and the use of emulsifying adjuvants [15].…”

“…For instance, S. suis protein candidates may behave as protective [14,22] or non-protective [12,28] immunogens at least in part depending on the adjuvant. Compared to human medicine, a wider range of adjuvants has been successfully used in commercial vaccines for animals and several new technologies are currently in preclinical development (reviewed in [29,30]).…”