Nasal immunization of humans with dehydrated liposomes containing Streptococcus mutans antigen

Abstract

Five healthy female adult volunteers were intranasally immunized twice (7-day interval) with 250 micrograms of a crude glucosyltransferase (GTF) preparation from Streptococcus mutans in liposomes. Parotid saliva, nasal wash, and serum were collected prior to and at weekly intervals for 6 weeks following the first immunization for analysis of anti-GTF activity by enzyme-linked immunosorbent assay. The levels of IgA1 anti-GTF activity increased in the nasal wash from all five individuals after immunization. Increases in salivary IgA1 and IgA2 anti-GTF activities were observed to a lesser extent. Increased serum IgM and IgA (but not IgG) anti-GTF activities were seen in immunized subjects. Nasal immunization with a dehydrated liposome-protein vaccine was effective in inducing an apparent secretory IgA antibody response, which was primarily of the IgA1 subclass. These results provide the first evidence of the effective use of a nasal liposome-protein vaccine in humans.

Humans Immunized with Streptococcus mutans Antigens by Mucosal Routes

“…This was a double-blind clinical study testing two forms of the vaccine antigen, i.e., soluble and liposomal antigens, and used a dose of E-GTF which was smaller than that previously used for nasal immunization . The results of this study and previous studies (Childers et al, 1997 provide evidence for the safety of both soluble and liposomal E-GTF for use in humans, and that these vaccines were immunogenic when given by the IN route. A significantly higher mean postimmunization IgA anti-E-GTF response was observed in nasal wash and parotid saliva but not in serum of the IN groups compared with the IT immunization groups.…”

“…Previous human studies designed to induce salivary IgA immune responses to S. mutans antigens have used the oral (Childers et al, 1991(Childers et al, , 1994Taubman, 1987, 1990) and nasal (Childers et al, 1997 routes for immunizations. Although results have been encouraging, salivary responses were variable, transient, and low in magnitude.…”

Dental Caries Vaccines: Prospects and Concerns

“…Parotid salivary IgA antibody responses, primarily of the IgA2 subclass, were induced in five of seven subjects. Similarly, nasal immunization with dehydrated liposomes containing this GTF preparation induced significant IgA1 antibody response in nasal washes (Childers et al, 1997(Childers et al, , 1999. Parotid salivary antibody levels to GTF were of lower magnitude.…”

Proteína de 18kDa de Mycobacterium leprae: um modelo de carregadora para vacinas de segunda geração

“…Embora os lipossomos tenham sido exaustivamente testados como veí-culos para drogas (Gregoriadis et al, 1996) e para vacinas, inclusive orais (Childers et al, 1997), há uma certa dificuldade em seu uso prático, devido à sua instabilidade (Crowe et al, 1985). Os problemas são os processos decorrentes da oxidação das cadeias hidrofóbicas insaturadas e da hidrólise da ligação entre o ácido graxo da cadeia hidrofóbica e a molécula de glicerofosfato, que levam a uma desestruturação dos lipossomos e ao vazamento do conteúdo aquoso interno (Zuidam & Crommelin, 1995;Memoli et ai., 1996).…”

“…Há estudos de outros sistemas de liberação controlada de imunógenos, como os lipossomos (Allison & Gregoriadis, 1974;Childers et al, 1997).…”