Differential kinetics and distribution of antibodies in serum and nasal and vaginal secretions after nasal and oral vaccination of humans

Abstract

Although nasal vaccination has emerged as an interesting alternative to systemic or oral vaccination, knowledge is scarce about the immune responses after such immunization in humans. In the present study, we have compared the kinetics and organ distribution of the antibody responses after nasal and oral vaccination. We immunized female volunteers nasally or orally with cholera toxin B subunit (CTB) and determined the specific antibody levels in serum and nasal and vaginal secretions, as well as the number of circulating antibody-secreting cells, before immunization and 1, 2, 3, 6, and 26 weeks thereafter. Nasal vaccination induced 9-fold CTB-specific immunoglobulin A (IgA) and 56-fold specific IgG antibody increases in nasal secretions, whereas no significant IgA increase was seen after oral vaccination. Both oral and nasal vaccination resulted in 5- to 6-fold CTB-specific IgA and 20- to 30-fold specific IgG increases in vaginal secretions. Strong serum responses to CTB were also induced by both routes of vaccination. A notable difference between nasal and oral vaccination was that the nasal route elicited a specific antibody response with a later onset but of much longer duration than did the oral route. We conclude from this study that the nasal route is superior to the oral route for administering at least nonliving vaccines against infections in the upper respiratory tract, whereas either oral or nasal vaccination might be used for eliciting antibody responses in the female genital tract.

FIG. 1

CTB-specific increases in serum IgA (A) and IgG (B), nasal secretion IgA (C) and IgG (D), and vaginal secretion IgA (E) and IgG (F) after two oral (POx2), two nasal (INx2), or a single nasal (INx1) vaccination. The individual titers, or titers adjusted to the total Ig content, from the time points before and at peak level after vaccination are shown. The statistical significance of the increases is shown as follows: ∗∗∗, P < 0.001; ∗∗, P < 0.01; ∗, P < 0.05; and ns, P > 0.05.

FIG. 2

CTB-specific ASCs per 10⁶ MNCs before (pre) and 1 (w1), 2 (w2), 3 (w3), and 4 (w4) or 6 (w6) weeks after two oral vaccinations, IgA (A) and IgG (B); two nasal vaccinations, IgA (C) and IgG (D); and a single nasal vaccination, IgA (E) and IgG (F).