Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina

Abstract

Forty-five volunteers were vaccinated twice intranasally with 10, 100, or 1,000 g of cholera toxin B subunit (CTB). Blood and nasal and vaginal secretions were collected before and 1 week after the second vaccination from all volunteers, and the specific and total immunoglobulin A (IgA) and IgG titers were determined by enzyme-linked immunosorbent assay. Samples were also taken 6 months (n ‫؍‬ 16) and 1 year (n ‫؍‬ 14) after the vaccination. The 10-and 100-g doses were well tolerated by the volunteers, but the 1,000-g dose induced increased secretions from the nose and repetitive sneezings for several hours. The CTB-specific serum IgA and IgG increased 21-and 7-fold, respectively, 1 week after vaccination with the medium dose and increased 61-and 37-fold, respectively, after the high dose. In nasal secretions the specific IgA and IgG increased 2-and 6-fold after the medium dose and 2-and 20-fold after the high dose, respectively. In vaginal secretions the specific IgA and IgG increased 3-and 5-fold after the medium dose and 56-and 74-fold after the high dose, respectively. The lowest dose did not induce any significant antibody titer increases in serum or in secretions. The specific IgA and IgG levels in secretions were still elevated after 6 months but were decreasing 1 year after the vaccination. These results show that intranasal vaccination of humans with CTB induces strong systemic and mucosal antibody responses and suggest that CTB may be used as a carrier for antigens that induce protective immunity against systemic as well as respiratory and genital infections.

Bronchus‐Associated Lymphoid Tissue (BALT) and Larynx‐Associated Lymphoid Tissue (LALT) are Found at Different Frequencies in Children, Adolescents and Adults

“…In humans, lymphoid structures have not been shown in the nose but Waldeyer's lymphoid ring is thought to be functionally active mucosa-associated lymphoid tissue [16]. There has recently been interest in intranasal vaccination and human studies have already been performed with success [26,27,28], although the actual site of antigen uptake is unclear. Therefore, the unknown LALT status in individuals should not discourage clinical trials with intranasal vaccination.…”

Effects of seven potential probiotic strains on specific immune responses in healthy adults: a double-blind, randomized, controlled trial

“…An ELISA method adapted from the GM1 dosage was used to determine serum-specific IgA, IgG and IgM and salivaryspecific IgA (Svennerholm & Holmgren, 1978;Svennerholm & Wiklund, 1983;Berquist et al, 1997). This method is based on the binding of cholera toxin to solid-phasecoupled GM1, utilizing the known affinity of this toxin for the cholera toxin receptor ganglioside GM1.…”

Induction of mucosal immune responses in the human genital tract

“…Intranasal immunization of women with recombinant CTB is of particular importance for induction of antibody responses in the genital tract secretions: doses of 100 and 1000 Wg of CTB were highly e¡ective for stimulating relatively high levels of speci¢c antibodies [37]. Studies of intranasal immunization with bacterial and viral vaccines and induction of antibodies in genital tract secretions are in progress in our laboratory [52].…”