Intranasal Vaccination with Pneumococcal Surface Protein A and Interleukin-12 Augments Antibody-Mediated Opsonization and Protective Immunity againstStreptococcus pneumoniaeInfection

Abstract

Streptococcus pneumoniae is a major pathogen in humans that enters the host primarily through the respiratory tract. Targeting mucosal surfaces directly may therefore be an optimal approach for vaccination to prevent bacterial colonization and invasive disease. We have previously demonstrated the effectiveness of interleukin-12 (IL-12) delivered intransally (i.n.) as an antiviral respiratory adjuvant. In this study, we examined the effects of i.n. IL-12 treatment on induction of protective humoral immunity against S. pneumoniae. Immunization i.n. with pneumococcal surface protein A (PspA) and IL-12 resulted in enhanced lung IL-10 mRNA expression and marked augmentation of respiratory and systemic immunoglobulin G1 (IgG1), IgG2a, and IgA antibody levels compared to those in animals receiving PspA alone. In addition, i.n. vaccination with PspA and IL-12 provided increased protection against nasopharyngeal carriage. Flow cytometric analysis revealed a threefold increase in antibody-mediated, complement-independent opsonic activity in the sera of PspA-and IL-12-treated animals, which was mainly contributed by IgG2a and, to a lesser extent, IgA. Passive transfer of these immune sera conferred complete protection from death upon systemic pneumococcal challenge. These findings demonstrate the effectiveness of combining PspA and IL-12 at mucosal sites to achieve optimal antibody-mediated opsonization and killing of S. pneumoniae.

IL-12 as an adjuvant for the enhancement of protective humoral immunity

“…In addition, intranasal vaccination with PspA and IL-12 provided increased protection against nasopharyngeal carriage. The aforementioned results were obtained using a T-dependent pneumococcal protein antigen as the vaccine but, importantly, similar results have been observed using pneumococcal and meningococcal polysaccharide vaccines, given either as T-dependent conjugate vaccines, for example Prevnar ® , or as T-independent nonconjugated vaccines, such as Pneumovax ® [23][24][25]28,32]. In both cases, it was found that IL-12 treatment at the time of immunization induced significantly elevated levels of IgG2a and IgG3 anti-polysaccharide antibodies in serum, as well as IgA and IgG antibodies in the lung.…”

“…For example, upon transfer of sera to naive recipients and intranasal challenge with a lethal dose of S. pneumoniae, all mice that received normal mouse serum succumbed to infection within 5 days, and mice receiving serum from animals vaccinated with pneumococcal surface protein A (PspA) alone showed no significantly increased protection [31]. Strikingly, every mouse that received serum from animals treated with both PspA and IL-12 survived the infection.…”

“…These include infections induced with influenza virus [22], Streptococcus pneumoniae [23][24][25], Francisella tularensis [26] and Yersinia pestis [Kumar D, Metzger DW, Unpublished Data]. We and others have repeatedly found that intranasal treatment of mice with IL-12 leads to increases in expression of both Th1-and Th2-associated antibodies in the serum [9][10][11][12][13][14] as well as in the lung [22][23][24][25][26][27]. In a typical experiment, mice are inoculated intranasally with vaccine only or vaccine plus IL-12.…”

Immunization with Polyamine Transport Protein PotD Protects Mice against Systemic Infection with Streptococcus pneumoniae

“…Proteins are, generally, antigenically conserved across all serotypes and stimulate a T-cell-dependent immune response resulting in more robust immunological memory (28). Several pneumococcal surface proteins have been shown to be effective immunogens and can prevent sepsis, pneumonia, and carriage in animal models (1,2,5,6,23,26).…”

Cationic pullulan nanogel as a safe and effective nasal vaccine delivery system for respiratory infectious diseases

“…24 In addition, co-administration of PspA antigen and IL-12 as a nasal adjuvant enhanced PspA-specific IgG and IgA responses, with increased protection from nasal carriage. 25 In addition, nasal immunization with chitosan–DNA nanoparticles that express PspA elicited protective immunity against nasal colonization by S. pneumoniae . 26 Furthermore, an antigen-delivery method has been developed that targets claudin-4, a major cell-adhesion molecule in tight junctions that is highly expressed on the epithelium of nasopharynx-associated lymphoid tissue.…”