Nasal vaccination with pneumococcal surface protein A in combination with cationic liposomes consisting of DOTAP and DC-chol confers antigen-mediated protective immunity against Streptococcus pneumoniae infections in mice

Tada, Rui; Suzuki, Haruo; Takahashi, Saeko; Negishi, Yoichi; Kiyono, Hiroshi; Kunisawa, Jun; Aramaki, Yukihiko

doi:10.1016/j.intimp.2018.06.027

Cited by 42 publications

(37 citation statements)

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“…The critical role of IL-17 in mucosal protection against S. pneumoniae has been well documented in many studies [47][48][49][50][51][52]. Specifically, IL-17 has been implicated in cross-protection against several S. pneumoniae serotypes [53][54][55][56].…”

Section: Discussionmentioning

confidence: 97%

Preclinical Efficacy of a Trivalent Human FcγRI-Targeted Adjuvant-Free Subunit Mucosal Vaccine against Pulmonary Pneumococcal Infection

Kumar

Sunagar²,

Gosselin

2020

Vaccines

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Lack of safe and effective mucosal adjuvants has severely hampered the development of mucosal subunit vaccines. In this regard, we have previously shown that immunogenicity of vaccine antigens can be improved by targeting the antigens to the antigen-presenting cells. Specifically, groups of mice immunized intranasally with a fusion protein (Bivalent-FP) containing a fragment of pneumococcal-surface-protein-A (PspA) as antigen and a single-chain bivalent antibody raised against the anti-human Fc-gamma-receptor-I (hFcγRI) elicited protective immunity to pulmonary Streptococcus pneumoniae infection. In order to further enhance the immunogenicity, an additional hFcγRI-binding moiety of the single chain antibody was incorporated. The modified vaccine (Trivalent-FP) induced significantly improved protection against lethal pulmonary S. pneumoniae challenge compared to Bivalent-FP. In addition, the modified vaccine exhibited over 85% protection with only two immunizations. Trivalent-FP also induced S. pneumoniae-specific systemic and mucosal antibodies. Moreover, Trivalent-FP also induced IL-17-and IL-22-producing CD4 + T cells. Furthermore, it was found that the hFcγRI facilitated uptake and presentation of Trivalent-FP. In addition, Trivalent-FP also induced IL-1α, MIP-1α, and TNF-α; modulated recruitment of dendritic cells and macrophages; and induced CD80/86 and MHC-II expression on antigen presenting cells.With over 90 known serotypes, Streptococcus pneumoniae remains the leading cause of community acquired pneumoniae. In addition, younger and immunocompromised populations are more vulnerable to infection. Furthermore, S. pneumoniae causes over 1 million deaths per year in children aged less than 5 years [10]. To date, two polysaccharide-based subunit vaccines are available to combat select serotypes. However, use of these 13 and 23 serotype vaccines cause serotype replacement in the vaccinated population [11]. This results in a surge of non-vaccine serotypes within the vaccinated population. Thus, new approaches to pneumococcal vaccines are required, which can generate protection over multiple serotypes. The pneumococcal surface protein A (PspA) has been known to induce cross-serotype protection against S. pneumoniae [12]. Thus, not only is S. pneumoniae a significant global health problem, it also expresses a well-defined protective protein antigen, making it a particularly suitable model to test and optimize our mucosal subunit vaccine platform.Previously we have shown that targeting vaccine antigens to antigen-presenting cells (APCs) eliminates the need for adjuvants.By genetically fusing a bivalent single-chain variable fragment-based antibody (Bivalent anti-human-Fc-gamma-receptor-I (FcγRI)), which specifically recognizes human-FcγRI, to a pneumococcal antigen (PspA), a fusion protein named Bivalent-FP was obtained ( Figure 1A). Bivalent-FP induces systemic and mucosal antibodies and protection against pulmonary S. pneumoniae infection by intranasal immunization. However, this vaccine requires at least three i...

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Section: Discussionmentioning

confidence: 97%

Preclinical Efficacy of a Trivalent Human FcγRI-Targeted Adjuvant-Free Subunit Mucosal Vaccine against Pulmonary Pneumococcal Infection

Kumar

Sunagar²,

Gosselin

2020

Vaccines

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“…Hence, we investigated the use of mucosal adjuvants, for the formulation of mucosal vaccines, to enhance an antigen-specific immune response in mucosa, which is crucial for developing effective split and/or subunit mucosal vaccines. In the course of our study, we found that cationic liposomes composed of DOTAP and DC-chol act as a potent mucosal adjuvant, resulting in both systemic and mucosal antigen-specific antibody responses in mice, when nasally co-immunized with an antigenic protein [12,15]. However, precise molecular mechanism(s) underlying the mucosal adjuvant effects of the cationic liposomes are still undetermined.…”

Section: Discussionmentioning

confidence: 82%

“…The cationic liposomes used in this study were prepared as previously described [12][13][14][15][16]. In short, 10 µmol of total lipids (DOTAP/DC-chol at 1:1 mol ratios) was evaporated to dryness in a glass tube and desiccated for 1 h in vacuo.…”

Section: Liposome Preparationmentioning

confidence: 99%

“…We have recently elucidated that intranasal vaccination of an antigenic protein with cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 3β-[N-(N ,N -dimethylaminoethane)-carbamoyl] (DC-chol) (DOTAP/DC-chol liposomes) induced antigen-specific mucosal and systemic antibody responses in mice [12][13][14]. Namely, the DOTAP/DC-chol liposome acts as a mucosal adjuvant for nasal vaccine formulations, especially for infectious diseases [15]. However, precise molecular mechanism(s) behind the mucosal adjuvant effects of cationic liposomes are still not clarified.…”

Section: Introductionmentioning

confidence: 99%

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Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity

et al. 2019

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Infectious disease remains a substantial cause of death. To overcome this issue, mucosal vaccine systems are considered to be a promising strategy. Yet, none are approved for clinical use, except for live-attenuated mucosal vaccines, mainly owing to the lack of effective and safe systems to induce antigen-specific immune responses in the mucosal compartment. We have reported that intranasal vaccination of an antigenic protein, with cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl], induced antigen-specific mucosal and systemic antibody responses in mice. However, precise molecular mechanism(s) underlying the mucosal adjuvant effects of cationic liposomes remain to be uncovered. Here, we show that a host double-stranded DNA (dsDNA), released at the site of cationic liposome injection, plays an essential role for the mucosal adjuvanticity of the cationic liposome. Namely, we found that nasal administration of the cationic liposomes induced localized cell death, at the site of injection, resulting in extracellular leakage of host dsDNA. Additionally, in vivo DNase I treatment markedly impaired OVA-specific mucosal and systemic antibody production exerted by cationic liposomes. Our report reveals that host dsDNA, released from local dying cells, acts as a damage-associated molecular pattern that mediates the mucosal adjuvant activity of cationic liposomes.

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“…In general, size, surface charge, and chemical composition of liposomes are important factors to be taken into consideration in the development of liposomes as the delivery system. However, limited studies of liposomes as an adjuvant in pneumococcal vaccine development have been published [156].…”

Section: Development Of Pneumococcal Nanovaccinesmentioning

confidence: 99%

Development of Next Generation Streptococcus pneumoniae Vaccines Conferring Broad Protection

et al. 2020

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Streptococcus pneumoniae is a major pathogen causing pneumonia with over 2 million deaths annually, especially in young children and the elderly. To date, at least 98 different pneumococcal capsular serotypes have been identified. Currently, the vaccines for prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes and are unable to protect against non-vaccine serotypes and unencapsulated S. pneumoniae. This has led to a rapid increase in antibiotic-resistant non-vaccine serotypes. Hence, there is an urgent need to develop new, effective, and affordable pneumococcal vaccines, which could cover a wide range of serotypes. This review discusses the new approaches to develop effective vaccines with broad serotype coverage as well as recent development of promising pneumococcal vaccines in clinical trials. New vaccine candidates are the inactivated whole-cell vaccine strain (Δpep27ΔcomD mutant) constructed by mutations of specific genes and several protein-based S. pneumoniae vaccines using conserved pneumococcal antigens, such as lipoprotein and surface-exposed protein (PspA). Among the vaccines in Phase 3 clinical trials are the pneumococcal conjugate vaccines, PCV-15 (V114) and 20vPnC. The inactivated whole-cell and several protein-based vaccines are either in Phase 1 or 2 trials. Furthermore, the recent progress of nanoparticles that play important roles as delivery systems and adjuvants to improve the performance, as well as the immunogenicity of the nanovaccines, are reviewed.

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Nasal vaccination with pneumococcal surface protein A in combination with cationic liposomes consisting of DOTAP and DC-chol confers antigen-mediated protective immunity against Streptococcus pneumoniae infections in mice

Cited by 42 publications

References 42 publications

Preclinical Efficacy of a Trivalent Human FcγRI-Targeted Adjuvant-Free Subunit Mucosal Vaccine against Pulmonary Pneumococcal Infection

Preclinical Efficacy of a Trivalent Human FcγRI-Targeted Adjuvant-Free Subunit Mucosal Vaccine against Pulmonary Pneumococcal Infection

Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity

Development of Next Generation Streptococcus pneumoniae Vaccines Conferring Broad Protection

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