Comparison of Immunogenicity and Protection of Two Pneumococcal Protein Vaccines Based on PsaA and PspA

Abstract

is a major cause of invasive pneumococcal disease, septicemia, and meningitis that can result in high morbidity rates in children under 5 years old. The current polysaccharide-based vaccines can provide type-specific immunity, but a broad-spectrum vaccine would provide greater coverage. Therefore, developing pneumococcal-protein-based vaccines that can extend to more serum types is highly important. In this study, we vaccinated mice via the subcutaneous (s.c.) route with a systemic vaccine that is a mixture of fusion protein PsaA-PspA23 and a single protein, PspA4, with aluminum hydroxide as an adjuvant. As a comparison, mice were immunized intranasally with a mucosal vaccine that is a mixture of PspA2-PA-BLP (where PA is protein anchor and BLP is bacterium-like particle) and PspA4-PA-BLP, via the intranasal (i.n.) route. The two immunization processes were followed by challenge with bacteria from two different PspA families. Specific IgG titers in the serum and specific IgA titers in the mucosa were determined following immunizations. Bacterial loads and survival rates after challenge were compared. Both the systemic vaccine and the mucosal vaccine induced a significant increase of IgG against PspAs. Only the mucosal vaccine also induced specific IgA in the mucosa. The two vaccines provided protection, but each vaccine showed an advantage. The systemic vaccine induced higher levels of serum antibodies, whereas the mucosal vaccine limited the bacterial load in the lung and blood. Therefore, coimmunizations with the two types of vaccines may be implemented in the future.

Intranasal Vaccination With Recombinant Antigen-FLIPr Fusion Protein Alone Induces Long-Lasting Systemic Antibody Responses and Broad T Cell Responses

“…Indeed, immunization of rOVA-FLIPr via intranasal administration induced long-lasting anti-OVA IgG and IgA antibody responses ( Figure 3 ). Many studies have shown that it is necessary to rely on mucosal vaccination to produce a strong IgA response ( 21 , 58 ). IgA exists in the circulatory system and the mucosal surface; the former exists in the form of monomer or polymer (pIgA), while the latter is in the form of a dimer and can be secreted to the mucosal surface (sIgA).…”

“…Extra adjuvant formulation is necessary for inducing robust immune responses. Novel mucosal adjuvants or a combination of traditional adjuvants may increase vaccine immunogenicity (20)(21)(22). Many adjuvants have been found to boost mucosal immune responses to antigens.…”

Progress in mucosal immunization for protection against pneumococcal pneumonia

“…PspA has been largely studied showing promising results in protection against pneumococcal lung infection in animal models [93][94][95][96][97][98]. Early studies ( Table 1) IgG to PspA [93,94].…”

Humoral immunity provided by a novel infectious bronchitis vaccine supplemented by bacterium-like particles (BLPs)

“…Their advantages comprise reducing secondary effects, the applicability of either a monovalent or a polyvalent vaccine, along with decreasing bacterial colonization and amplification in the lungs, being easily administered for mass immunization, not requiring booster immunization, triggering both the systemic and mucosal immune systems, possessing a higher binding capacity, as well as less anticarrier response, when compared to to a living lactic acid bacteria (LAB) [13]. Surprisingly, their capacity for being stored without the need for a cold chain over a long period of time was also noticeable [14]. BLPs are able to reduce the bacterial load in the lungs [14].…”

“…Surprisingly, their capacity for being stored without the need for a cold chain over a long period of time was also noticeable [14]. BLPs are able to reduce the bacterial load in the lungs [14]. Additionally, it was found that when a secondary bacterial infection also existed, the mortality of young chickens caused by IBV was higher [15].…”