Adjuvanticity and protective immunity elicited by Bordetella pertussis antigens encapsulated in poly(DL-lactide-co-glycolide) microspheres

Abstract

Bordetella pertussis antigens, encapsulated in biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) microspheres, were evaluated for their immunogenicity and ability to elicit a protective immune response against B. pertussis respiratory infection. Microencapsulated pertussis toxoid, filamentous hemagglutinin, and pertactin all retained their immunogenicity when administered parenterally. Intranasal immunization with a low dose (1 g) of encapsulated filamentous hemagglutinin, pertussis toxoid, or pertactin elicited strong specific immunoglobulin G and immunoglobulin A antibody responses in respiratory secretions that were greater in magnitude than the responses elicited by the same doses of unencapsulated antigen. Intranasal immunization with as little as 1 g of encapsulated pertussis antigen prior to infection reduced the bacterial recovery by 3 log 10 CFU. However, intranasal immunization with the same low doses of unencapsulated antigens did not reduce infection. Intranasal administration of a combination of 1 g of each of the microencapsulated pertussis antigens was more effective in reducing bacterial infection than administration of any single microencapsulated antigen. Intranasal administration of microencapsulated B. pertussis antigens elicits high levels of specific antibody coinciding with protection against infection when these microspheres are administered to the respiratory tract. These data provide evidence of the respiratory adjuvanticity of three different DL-PLG microsphere preparations, each of which contains a unique B. pertussis antigen.

Protective Immunity to Bordetella pertussis Requires Both B Cells and Cd4+ T Cells for Key Functions Other than Specific Antibody Production

“…All of the immunized mice had no detectable bacteria in lungs or tracheae at 7 d after challenge. In contrast to our previous studies using microencapsulated purified pertussis antigens, which elicited high levels of antigen-specific IgG and IgA in serum and secretions (25), two intranasal immunizations with 30 g FFBP did not induce consistent levels of specific serum IgG or IgA to purified pertussis antigens FHA, PRN, pertussis toxin (PT), lipooligosaccharide (LOS), or fimbriae (Table II). In studies of Ͼ30 individual animals, occasional small IgG serum antibody responses to all individual antigens were observed (data not shown).…”

“…223-94-1237 by the Southern Research Institute. The encapsulated microspheres were characterized and had properties similar to those described previously (25).…”

“…The ability of various antibody preparations, including one shown previously to transfer protection (25), to protect mice against a B. pertussis infection by passive immunization was then evaluated. As shown in Table III, mice that received the serum antibody to the microsphere combination completely cleared the infection in both the lungs and tracheae by 7 d after the challenge.…”

Intranasal immunization of mice with herpes simplex virus type 2 recombinant gD2: the effect of adjuvants on mucosal and serum antibody responses

“…In previous studies involving intranasal immunization with bacterially derived proteins 26,27 or a chemically toxoided antigen28 microparticles were shown to induce protective immunity in mice against aerosol challenge. The current studies demonstrated that microparticles are also an effective mucosal adjuvant for intranasal immunization with an entrapped recombinant protein.…”

Nasal Lymphoid Tissue (NALT) as a Mucosal Immune Inductive Site

“…immunization in inducing generalized mucosal immune responses [2][3][4]. Intranasal immunization can establish effective immunity against pneumococcal colonization in the upper respiratory tract, as well as protect mice from intratracheal challenge with virulent strains of pneumococci [5], block pharyngeal colonization by group A streptococci [6], protect mice from influenza virus infection [7], reduce Bordetella pertussis infection in mice [8], protect mice from i.n. herpes simplex virus challenge [9], and protect against Streptococcus mutans colonization on tooth surfaces [10,11].…”