Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response
Dw. Pascual et al., Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response, INFEC IMMUN, 67(12), 1999, pp. 6249-6256
Protective immunity to enterotoxigenic Escherichia coli (ETEC) is antibody
(Ab) dependent; however, oral immunization with purified ETEC fimbriae fail
s to elicit protective immunity as a consequence of antigenic alteration by
the gastrointestinal (GI) tract. Unless unaltered ETEC fimbriae can reach
the inductive lymphoid tissues of the GI tract, immunity to ETEC cannot be
induced, To produce immunity, live vectors, such as Salmonella typhimurium,
can effectively target passenger antigens to the inductive lymphoid tissue
s of the GI tract. By convention, oral immunizations with Salmonella vector
s induce CD4+ T helper (Th) cell responses by gamma interferon (IFN-gamma)-
dominated pathways both to the vector and passenger antigen, resulting in s
erum immunoglobulin G2a (IgG2a) and modest mucosal IgA Ab responses, In the
present study, mice orally immunized with a Salmonella vector engineered t
o stably express ETEC colonization factor antigen I (CFA/I) showed initiall
y elevated serum IgG1 and mucosal IgA anti-CFA/I Ab responses. As expected,
mice orally immunized with an E. coli-CFA/I construct elicited poor anti-C
FA/I Ab responses. In fact, the addition of cholera toxin during oral E, co
li-CFA/I immunization failed to greatly enhance mucosal IgA Ab responses. S
even days after immunization with the Salmonella-CFA/I construct, cytokine-
specific ELISPOT showed induction of predominant Th2-type responses in both
mucosal and systemic immune compartments supporting the early IgG1 and IgA
anti-CEA/I Abs, By 4 weeks, the Th cell response became Th1 cell dominant
from the earlier Th2-type responses, as evidenced by increased mucosal and
systemic IFN-gamma-producing T cells and a concomitant elevation of serum I
gG2a Ab responses. This biphasic response offers an alternative strategy fo
r directing Salmonella vector-induced host immunity along a Th2 cell-depend
ent pathway, allowing for early promotion of mucosal and systemic Abs.