Immunity after intranasal immunization

Immunity after Intranasal Immunization 5.6.93 Need for Adjuvants... 

Chatel, J. M., Langella, P, Adel-Patient, K., Commissaire, J., Wal, J. M., and Corthier, G. (2001), Induction of mucosal immune response after intranasal or oral inoculation of mice with Lactococcus lactis producing bovine beta-lactoglobulin, Clin. Diag. Lab. Immunol., 8, 545-551. 

Lovgren, K., Kaberg, H., and Morein, B. (1990), An experimental influenza subunit vaccine (iscom) Induction of protective immunity to challenge infection in mice after intranasal or subcutaneous administration, Clin. Exp. Immunol., S2,435-439. 

Intranasal vaccination route has received growing interest for non-invasive immunization. Intranasal immrmization has been quite effective for various vaccine-delivery systems. Both solution and microsphere formulations tend to show good immune responses after intranasal administration. Immunization of mice with tetanus toxoid, in solution and microsphere-encapsulated... 

KATZ, J HARMON, C.C., BUCKNER, G.P., RICHARDSON, G.J., RUSSELL, M.W. MICHALEK, S.M. (1993) Protective salivary immunoglobulin A responses against Streptococcus mutans infection after intranasal immunization with S. mutans antigen I/II coupled to the B subunit of cholera toxin. Infection and Immunity, 61, 1964—1971. 

Baudner, B.C., Verhoef, J.C., Giuhani, M.M. et al. 2005. Protective immune responses to meningococcal C conjugate vaccine after intranasal immunization of mice with the LTK63 mutant plus chitosan or trim-ethyl chitosan chloride as novel dehvery platform. J. Drug Target. 13 489-498. 

Poly(ethylene glycol) (PEG)-coated poly(lactic acid) (PLA) nanoparticles were synthesized and tested for their ability to load tetanous toxoid, to deliver it in an active form, and to transport it across the nasal and intestinal mucosa. It was observed that PEG coating improved the stability of PLA nanoparticles in the gastrointestinal fluids and helped the transport of the encapsulated tetanus toxoid across the intestinal and nasal mucosa. Aditionally, a high and long-lasting immune response was reported after intranasal administration of this nanoparticulate formulation [56]. 

Gutierro I, Hernandez RM, Igartua M et al (2002) Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres. Vaccine 21 67-77... 

Johansson, E.L., et al. 1998. Antibodies and antibody secreting cells in the female genital tract after vaginal or intranasal immunization with cholera toxin B subunits or conjugate. Infect Immunol 66 514. 

The route of administration influences the likelihood of an antibody response independent of the mechanism of induction. The probability of an immune response is the highest with subcutaneous administration, less probable after intramuscular administration and intravenous administration is the least immunogenic route. There are no studies comparing parenteral and nonparenteral routes of administration. Flowever, as both mucosal tissues and the skin are immune competent organs designed to keep invaders out of the body, intranasal, pulmonary, and transdermal administration of therapeutic proteins may increase the risk of an immune response as compared to parenteral routes. 

In a randomized, double-blind study, trivalent, live, attenuated, cold-adapted intranasal influenza vaccine (FluMist) has been compared with intranasal placebo plus a trivalent injected inactivated influenza vaccine (5). The 200 patients were aged 65 years and over and had chronic cardiovascular or pulmonary conditions or diabetes mellitus. During the 7 days after immunization, sore throat was reported on at least one day by significantly more of the FluMist recipients (15 versus 2%). The increased frequency of sore throat may have been attributable to direct or indirect effects of vaccine virus replication. No other symptom was associated with FluMist. These findings were consistent with evaluations of other live, attenuated, cold-adapted influenza vaccine formulations in older adults. However, further studies of the safety of FluMist are warranted. 

The current status of adjuvanted influenza vaccines has been reviewed (26). The authors concluded that the vaccine produces a higher titer of antibodies than non-adjuvanted or virosomal vaccines. Local reactions occur more often, but are mild and transient. The results of a trial with two doses of an intranasally administered inactivated virosome-formulated influenza vaccine containing Escherichia coli heat-labile toxin as a mucosal adjuvant in 106 volunteers aged 33-63 years have been reported (27). About 50% of vaccinees had local adverse reactions (44% after the first dose and 54% after the second dose) or systemic adverse reactions (48 and 46%) after administration of the vaccine. Rhinorrhea, sneezing, and headache were the most common reactions they were mild and transient and resolved within 24-48 hours. No febrile reactions were associated with immunization. Between 77 and 92% of vaccinees developed protective hemagglutination inhibition antibody titers against the two influenzae A strains of the vaccine, whereas protective antibody titers against the B strain of the vaccine were achieved in only 49-58%. 

Other chemical inducers, such as pyran copolymers, tilorone, diethylaminoethyl dextran, and heparin, also have been used. Tilorone is an effective inducer of interferon in mice, but it is relatively ineffective in humans. Initial use of interferon and its inducers instilled intranasally after rhinovirus exposure was successful in the prevention of respiratory diseases. The clinical success of interferon and its inducers has not yet been established, although they may play a significant role in cell-mediated immunity to viral infections and cancer. Disadvantages of interferon use include unacceptable side effects, such as fever, headache, myalgias, leukopenia, nausea, vomiting, diarrhea, hypotension, alopecia, anorexia, and weight loss. 

Myc A, Kukowska-LataUo JF, Biehnska AU, Cao P, Myc PP, Janczak K, Sturm TR, Grabinski MS, Landers JJ, Young KS, Chang J, Hamouda T, Olszewski MA, Baker JR (2003) Development of immune response that protects mice from viral pneumonitis after a single intranasal immunization with influenza A virus and nanoemulsion. Vaccine. 21 3801-3809. 

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