Respiratory Immunity in Rabbits. Vii. Resistance to Intranasal Infection in the Absence of Demonstrable Antibodies*

Büll, Christian; McKee, Clara M.

doi:10.1093/oxfordjournals.aje.a121662

Cited by 16 publications

(13 citation statements)

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“…Protection elicited by intranasally applied killed whole cells was reported in 1928 (9,24) and confirmed in recent studies (16,27). An important aspect of our studies, however, is that the immunizing strain is unencapsulated.…”

Section: Discussionsupporting

confidence: 77%

Intranasal Immunization with Killed Unencapsulated Whole Cells Prevents Colonization and Invasive Disease by Capsulated Pneumococci

Malley

Lipsitch

Stack³

et al. 2001

Infect Immun

166

190

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A whole-cell killed unencapsulated pneumococcal vaccine given by the intranasal route with cholera toxin as an adjuvant was tested in two animal models. This vaccination was highly effective in preventing nasopharyngeal colonization with an encapsulated serotype 6B strain in mice and also conferred protection against illness and death in rats inoculated intrathoracically with a highly encapsulated serotype 3 strain. When the serotype 3 challenge strain was incubated in the sera of immunized rats, it was no longer virulent in an infant-rat sepsis model, indicating that the intranasal immunization elicited protective systemic antibodies. These studies suggest that killed whole-cell unencapsulated pneumococci given intranasally with an adjuvant may provide multitypic protection against capsulated pneumococci.Streptococcus pneumoniae (pneumococcus) annually causes 10 million deaths worldwide, including the deaths of 1 million children in low-income countries (26). Type-specific immunity, based on the capsular polysaccharides (PS), is well established (20). The licensed 23-valent PS vaccine, however, is not efficacious in children younger than 2 years. The newly licensed heptavalent PS conjugate vaccine protects against 90% of pneumococcal invasive disease in infancy in the United States (28) but includes fewer serotypes than the PS vaccine and omits several that are prevalent worldwide (10). Other drawbacks of the conjugate vaccine include a limited effect on otitis media (2, 11), high costs, and the potential for serotype replacement, which has already been suggested in recent clinical trials (11, 17; R. Dagan, N. Givon, P. Yagupsky, N. Porat, J. Janco, I. Chang, et al., Program Abstr. 38th Intersci. Conf. Antimicrob. Agents Chemother., abstr. S52, 1998).Several investigators have identified protective antigens common to pneumococci of many or all serotypes. Several such "species" antigens in purified or vectored form have shown protection in animal models (4-6, 8, 18, 19, 23, 25), but it is uncertain whether, when, and at what cost any of these will be developed as an effective vaccine for humans, particularly in low-income countries. As an alternative presentation of species antigens, we have studied unencapsulated whole cells, which should present a number of such antigens in native configuration unoccluded by capsule. In addition, the intranasal route of immunization might elicit mucosal immunity and, with suitable adjuvant, systemic immunity as well. Finally, of importance to low-income countries, a mucosally administered whole-cell preparation has the possible advantage of low cost of production and administration, without the need for sterile injection devices. In the present study we tested killed, unencapsulated cells applied intranasally with cholera toxin (CT) as an adjuvant (R. Malley, S. Pelton, A. Stack, R. Saladino, D. E. Briles, and P. Anderson, 2nd Int. Symp. Pneumococci Pneumococcal Dis., abstr. P25, 2000), using two animal models: nasopharyngeal colonization of mice with type 6B and lethal intrat...

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Section: Discussionsupporting

confidence: 77%

Intranasal Immunization with Killed Unencapsulated Whole Cells Prevents Colonization and Invasive Disease by Capsulated Pneumococci

Malley

Lipsitch

Stack³

et al. 2001

Infect Immun

166

190

View full text Add to dashboard Cite

show abstract

“…The work of Askonas and Humphrey [1] referred to above showed that the lung was involved in the gene- [39] showed that after administration of antigen into the respiratory tract of rabbits a local immune response occurred, un accompanied by serum antibody. Furthermore, this response appeared to correlate better with effective resistance to the challenging organism (pneumococ cus) than the presence of serum antibody.…”

Section: Immune Responsesmentioning

confidence: 97%

Bronchus-Associated Lymphoid Tissue

Bienenstock¹

1985

Int Arch Allergy Immunol

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“…His extensive studies were published in a classical monograph on local immunity (Besredka 1927). These observations are reminiscent of experiments performed by Bull and McKee (1929) who intranasally immunized rabbits with a killed pneumococcal vaccine before a challenge with a virulent pneumococcus. In comparison with control animals or those immunized with a single dose, two to four immunizations were sufficient to prevent fatal pneumonia and septicemia (Table 1).…”

Section: Historical Aspectsmentioning

confidence: 73%

“…An admittedly incomplete list of other microorganisms that have been used in oral vaccines in veterinary and human medicine provides convincing evidence that confirms the feasibility of this approach (Mestecky 1987) (Table 2). Of greater interest are recent studies summarized elsewhere (Mestecky 1987) (Calmette andGuerin 1906-1923) Secretory and serum antibodies, some protection (Besredka 1919(Besredka -1927 Oral immunization preferable to systemic (Vaillant 1922) Oral vaccine now available (Levine 1987) Protection achieved by intranasal immunization (Bull and McKee 1929) Antibodies in milk (Goldblum et al 1975) S-IgA antibodies in saliva and tears Serum antibodies (Magnus 1908) Decrease in systemic reactivity (Wells and Osborne 1911) Inhibition of skin reactivity (Chase 1946) Serum and secretory antibodies, improved clinical symptoms (Bjorksten et al 1986;Taudorf et al 1987;Wheeler et al 1987;Waldman and Bergmann 1987) No effect; others observed partial or complete protection (Dakin 1822;Schamberg 1925;Shelmire 1941;Zisserman 1941;Gold and Masucci 1942) "Assembled from Bjorksten and Dewdney 1987;Bull and McKee 1929;Chase 1946;Dakin 1829;Gay 1924; Holmgren this volume, International symposium on vaccination of man and animals by the non-parenteral route 1976; Levine et al 1987;Mestecky 1987;Platts-Mills 1987;Stevens 1945;Tomasi 1980;and Wells and Osborne 1911. The interest in oral desensitization by plant extract was revived in this country at the end of the last century and lasted until the end of the Second World War (for review see Stevens 1945). In many studies, dermatologist treated their patients with alcohol, ether, or acetone extracts...…”

Section: Historical Aspectsmentioning

confidence: 99%