Nasal vaccination with attenuated Salmonella typhimurium strains expressing the Hepatitis B nucleocapsid: dose response analysis
2001; Elsevier BV; Volume: 19; Issue: 20-22 Linguagem: Inglês
10.1016/s0264-410x(01)00009-3
ISSN1873-2518
AutoresDenise Nardelli‐Haefliger, Jalil Benyacoub, Robert Lemoine, Sally Hopkins-Donaldson, Alexandra Potts, Françoise Hartman, Jean‐Pierre Kraehenbuhl, P. De Grandi,
Tópico(s)Hepatitis B Virus Studies
ResumoNasal vaccination of mice with recombinant attenuated strains of Salmonella typhimurium is more efficient at inducing antibody responses than oral vaccination. However, mortality was observed when high doses [109 colony forming unit (CFU)], otherwise safe by the oral route, were administered. This observation was counterbalanced by the fact that nasal vaccination was still highly efficient with lower doses (106 CFU), which are inefficient by the oral route and this, without any incidents of mortality. Here, we further analyse in mice the effect of nasal vaccination with differently attenuated S. typhimurium strains expressing the Hepatitis B nucleocapsid (HBc). Surprisingly, as few as 100 CFU were sufficient to induce a maximal HBc specific antibody response, but only if the bacteria were inhaled. Furthermore, we observed no correlation between the inoculum dose and the number of surviving bacteria in cervical lymph nodes and spleen. Examination of lung sections revealed strong inflammation and bronchopneumonia 24 h after nasal vaccination with 108 CFU, while only minor signs of inflammation were detected transiently when 103 CFU or phosphate buffered saline (PBS) were administered. Our data suggest that the safety issue of nasal vaccination with low doses of the Salmonella vaccine strains should be addressed in humans, as it might be an efficient alternative to oral vaccination.
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