scholarly journals Cross-Protective Immunity of Mice Induced by Oral Immunization with Pneumococcal Surface Adhesin A Encapsulated in Microspheres

2002 ◽  
Vol 70 (3) ◽  
pp. 1143-1149 ◽  
Author(s):  
Jun-Young Seo ◽  
Seung Yong Seong ◽  
Byung-Yoon Ahn ◽  
Ick Chan Kwon ◽  
Hesson Chung ◽  
...  
Keyword(s):  
Immune System ◽  
Oral Delivery ◽  
Protective Immunity ◽  
Capsular Polysaccharide ◽  
Oral Vaccine ◽  
Pneumococcal Infection ◽  
The Elderly ◽  
Oral Immunization ◽  
Mucosal Antibody ◽  
Lung Colonization

ABSTRACT The global use of a capsular polysaccharide-based pneumococcal vaccine has been limited because of serotype-specific protection and poor effectiveness in individuals with low immunocompetency. The mucosal immune system develops earlier in infants and lasts longer in the elderly than does the systemic immune system. Furthermore, mucosal immunization is beneficial for AIDS patients, because human immunodeficiency virus-infected subjects can develop normal mucosal antibody responses even in late clinical phases. For these reasons, we evaluated recombinant pneumococcal surface adhesin A (rPsaA) of Streptococcus pneumoniae in terms of cross-protective immune responses after oral delivery. Encapsulated rPsaA provided higher immunogenicity than naked rPsaA. Coencapsulation or codelivery of the cholera toxin (CT) B subunit (CTB) and CT also increased the immunogenicity of rPsaA. Cross-protective immunities against five strains of S. pneumoniae (types 4, 6B, 14, 19F, and 23F) were induced after oral immunization with microencapsulated rPsaA. Lung colonization and septicemia caused by the five serotypes were significantly inhibited by oral immunization with microencapsulated rPsaA. These results suggest that rPsaA coencapsulated with CTB can be used as an oral vaccine to induce cross-protective immunity for the prevention of pneumococcal infection.

Immune system changes and immunosenescence

2017 ◽  
pp. 331-336
Author(s):  
Graham Pawelec ◽  
Ludmila Müller ◽  
Tamas Fülöp ◽  
Deborah Dunn-Walters
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Older People ◽  
Protective Immunity ◽  
Elderly Population ◽  
Immune Status ◽  
The Elderly ◽  
Degenerative Diseases ◽  
System Changes ◽  
Increased Susceptibility

The immune system defends against infection, but older people paradoxically suffer not only from failing immunity resulting in increased susceptibility to infections and decreased responsiveness to vaccination, but at the same time increased inflammation and immunopathology accompanying immune responses. Interventions to reduce such deleterious effects while enhancing protective immunity are challenging but need to be confronted if we are to deal successfully with the increasing numbers of elderly and frail people in modern societies. To do this, we need to understand the mechanisms responsible for age-associated increased susceptibility to infections and immune-influenced chronic degenerative diseases of ageing. Defining relevant age-associated alterations and identifying reliable biomarkers for monitoring clinically-relevant immune status in the elderly population is crucial to overcoming these problems. Here, we briefly outline age-associated changes to immunity collectively termed ‘immunosenescence’.

Oral immunization with recombinant Lactococcus lactis confers protection against respiratory pneumococcal infection

2008 ◽  
Vol 54 (10) ◽  
pp. 845-853 ◽  
Author(s):  
Julio Villena ◽  
Marcela Medina ◽  
Raúl Raya ◽  
Susana Alvarez
Keyword(s):  
Lactococcus Lactis ◽  
Protective Immunity ◽  
Protein A ◽  
Pneumococcal Infection ◽  
Interferon Γ ◽  
Oral Immunization ◽  
Interleukin 4 ◽  
Cell Counts ◽  
Recombinant Lactococcus Lactis ◽  
Th1 And Th2 Responses

In the present work, we evaluated if oral immunization with the pneumococcal protective protein A (PppA), expressed in the cell wall of Lactococcus lactis (L. lactis PppA+), was able to confer protective immunity against Streptococcus pneumoniae . Mice were immunized orally with L. lactis PppA+ for 5 consecutive days. Vaccination was performed one (nonboosted group) or 2 times with a 2 week interval between each immunization (boosted group). Oral priming with L. lactis PppA+ induced the production of anti-PppA IgM, IgG, and IgA antibodies in serum and in bronchoalveolar (BAL) and intestinal (IF) lavage fluids. Boosting with L. lactis PppA+ increased the levels of mucosal and systemic immunoglobulins. Moreover, the avidity and the opsonophagocytic activity of anti-PppA antibodies were significantly improved in the boosted group. The presence of both IgG1 and IgG2a anti-PppA antibodies in serum and BAL and the production of both interferon γ and interleukin-4 by spleen cells from immunized mice indicated that L. lactis PppA+ stimulated a mixture of Th1 and Th2 responses. The ability of L. lactis PppA+ to confer cross-protective immunity was evaluated using challenge assays with serotypes 3, 6B, 14, and 23F. Lung bacterial cell counts and hemocultures showed that immunization with L. lactis PppA+ improved resistance against all the serotypes assessed, including serotype 3, which was highly virulent in our experimental animal model. To our knowledge, this is the first demonstration of protection against respiratory pneumococcal infection induced by oral administration of a recombinant lactococcal vaccine.

scholarly journals Liposomal encapsulation of polysaccharides (LEPS) as an effective vaccine strategy to protect aged hosts against S. pneumoniae infection

2021 ◽  
Author(s):  
Manmeet Bhalla ◽  
Roozbeh Nayerhoda ◽  
Essi Y. I Tchalla ◽  
Alexsandra Abamonte ◽  
Dongwon Park ◽  
...  
Keyword(s):  
Pneumococcal Disease ◽  
Complex Disease ◽  
Capsular Polysaccharide ◽  
Pneumococcal Infection ◽  
The Elderly ◽  
Effective Vaccine ◽  
Pneumococcal Infections ◽  
Vaccine Strategy ◽  
Vaccine Platform ◽  
Old Mice

Despite the availability of licensed vaccines, pneumococcal disease caused by the bacteria Streptococcus pneumoniae (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts elderly individuals ≥65 years old. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against S. pneumoniae, with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2-3 months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (20-22 months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.

scholarly journals Acquired, but Not Innate, Immune Responses to Streptococcus pneumoniae Are Compromised by Neutralization of CD40L

2000 ◽  
Vol 68 (2) ◽  
pp. 511-517 ◽  
Author(s):  
Young-il Hwang ◽  
Moon H. Nahm ◽  
David E. Briles ◽  
David Thomas ◽  
Jeffrey M. Purkerson
Keyword(s):  
Streptococcus Pneumoniae ◽  
Capsular Polysaccharide ◽  
Pneumococcal Infection ◽  
Systemic Infection ◽  
Humoral Response ◽  
Nasal Carriage ◽  
The Elderly ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
Cell Wall Polysaccharides

ABSTRACT Streptococcus pneumoniae is a significant pathogen of young children and the elderly. Systemic infection by pneumococci is a complex process involving several bacterial and host factors. We have investigated the role of CD40L in host defense against pneumococcal infection. Treatment of mice with MR-1 antibody (anti-CD154/CD40L) markedly reduced antibody responses to the pneumococcal protein PspA, elicited by immunization of purified protein or whole bacteria. In mice immunized with whole bacteria, MR-1 treatment reduced antibody responses to capsular polysaccharides but not cell wall polysaccharides. MR-1 did not suppress antibody responses to isolated capsular polysaccharides but did reduce the production of antibody to a capsular polysaccharide-protein conjugate, indicating that when presented in the context of whole bacteria, the humoral response to capsular polysaccharides is partially T-cell dependent. Despite the reduction of the protective humoral responses to pneumococcal infection, administration of MR-1 had no effect on sepsis, lung infection, or nasal carriage in nonimmune mice inoculated with virulent pneumococci. Thus, short-term neutralization of CD40L does not compromise innate host defenses against pneumococcal invasion.

scholarly journals Boosting of Cellular Immunity against Mycobacterium tuberculosis and Modulation of Skin Cytokine Responses in Healthy Human Volunteers by Mycobacterium bovis BCG Substrain Moreau Rio de Janeiro Oral Vaccine

2006 ◽  
Vol 74 (4) ◽  
pp. 2449-2452 ◽  
Author(s):  
Catherine A. Cosgrove ◽  
Luiz R. R. Castello-Branco ◽  
Tracy Hussell ◽  
Amy Sexton ◽  
Rafaela Giemza ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rio De Janeiro ◽  
Protective Immunity ◽  
Oral Vaccine ◽  
Oral Immunization ◽  
Healthy Human ◽  
Purified Protein Derivative ◽  
Cytokine Responses ◽  
Human Volunteers ◽  
Interferon Responses

ABSTRACT Oral immunization of healthy adults with 107 CFU BCG Moreau Rio de Janeiro was well tolerated and significantly boosted gamma interferon responses to purified protein derivative, Ag85, and MPB70 from previous childhood intradermal BCG immunization. Oral BCG offers the possibility of a needle-free tuberculosis vaccine and of boosting the protective immunity from intradermal tuberculosis vaccines.

scholarly journals Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts Against S. pneumoniae Infection

2021 ◽  
Vol 2 ◽  
Author(s):  
Manmeet Bhalla ◽  
Roozbeh Nayerhoda ◽  
Essi Y. I. Tchalla ◽  
Alexsandra Abamonte ◽  
Dongwon Park ◽  
...  
Keyword(s):  
Pneumococcal Disease ◽  
Complex Disease ◽  
Capsular Polysaccharide ◽  
Pneumococcal Infection ◽  
The Elderly ◽  
Effective Vaccine ◽  
Pneumococcal Infections ◽  
Vaccine Strategy ◽  
Vaccine Platform ◽  
Old Mice

Despite the availability of licensed vaccines, pneumococcal disease caused by the bacteria Streptococcus pneumoniae (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts older adults aged ≥65 years. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against S. pneumoniae, with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2–3 months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (18–22 months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.

scholarly journals Pneumococcal Diversity: Considerations for New Vaccine Strategies with Emphasis on Pneumococcal Surface Protein A (PspA)

1998 ◽  
Vol 11 (4) ◽  
pp. 645-657 ◽  
Author(s):  
David E. Briles ◽  
Rebecca Creech Tart ◽  
Edwin Swiatlo ◽  
Joseph P. Dillard ◽  
Patricia Smith ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Protein A ◽  
Pneumococcal Infection ◽  
Significant Risk ◽  
Surface Protein ◽  
Infectious Agent ◽  
The Elderly ◽  
Multidrug Resistant ◽  
Pneumococcal Surface Protein A ◽  
Potential Vaccine

SUMMARY Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to human health has been underscored by the recent rise in the frequency of isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly is common and often fatal. Young children in the developing world are at significant risk for fatal pneumococcal respiratory disease, while in the developed world otitis media in children results in substantial economic costs. Immunocompromised patients are extremely susceptible to pneumococcal infection. With 90 different capsular types thus far described, the diversity of pneumococci contributes to the challenges of preventing and treating S. pneumoniae infections. The current capsular polysaccharide vaccine is not recommended for use in children younger than 2 years and is not fully effective in the elderly. Therefore, innovative vaccine strategies to protect against this agent are needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules are being investigated as potential vaccine candidates. Pneumococcal surface protein A (PspA) has been evaluated for its ability to elicit protection against S. pneumoniae infection in mouse models of systemic and local disease. This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains. These parameters will be critical to the design of broadly protective pneumococcal vaccines.

scholarly journals 10. Kinetics of Post-Vaccination Seroprotection to S. Pneumonia for the Immune-Compromised and Vaccine-Naïve Populations

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S27-S28
Author(s):  
Jeffrey Gruenglas ◽  
James Mond ◽  
Micaela Scobie ◽  
Cynthia Tolman ◽  
Joseph Martinez
Keyword(s):  
Capsular Polysaccharide ◽  
The Elderly ◽  
Community Acquired Pneumonia ◽  
Prior History ◽  
Antibody Activity ◽  
Vaccine Response ◽  
Serum Samples ◽  
Opsonic Activity ◽  
And Control

Abstract Background S. pneumonia infection presents a significant challenge, accounting for 20–38% of hospital-acquired pneumonia, and the leading cause of community-acquired pneumonia despite availability of effective vaccines. Incidence is highest in children under 2 years, the immunocompromised, and elderly. CDC has reported the emergence of antibiotic resistance in ~30% of cases, adding to risk of morbidity and mortality. Fewer than half of the elderly are vaccinated and vulnerable to infection on admission. Passive immunotherapy as an adjunct to vaccines may improve outcomes in such populations. The objective of this study was to evaluate whether seroprotective response induced with a pneumococcal conjugate vaccine could rapidly yield protective opsonic levels of antibody within anticipated duration of hospitalization. Methods Healthy donors (n=30) were immunized with Prevnar. Blood was drawn on days 0, 3, 7, 10, 14, 21, and 28. Samples were pooled and tested for presence of functional opsonic antibodies recognizing capsular polysaccharides. Clearance mechanism of S. pneumonia was based on antibody recognition to pneumococcal capsular polysaccharide and opsonic titers used as an in vitro surrogate to evaluate the efficacy of vaccine. Results There was little to no opsonic activity against most serotypes on day 0, except for low antibody activity with serotypes 1, 3, 4, and 5. Titers increased, with protective levels achieved by day 10 for most serotypes (except 14 and 18C), peaking at day 14 or after across serotypes (Figures 1 and 2). Average titers rose from log2 titer 2 on day 0 to log2 titer 8 on days 21 and 28. Titers against most serotypes reached log2 10 (titer 1024) or higher. Patients remained susceptible to nosocomial infection for at least 10 days post admission until protective titers are reached. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V. N=2. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 14, 18C, 19A, 19F, and 23F. N=2. Conclusion Patients with no prior history of vaccination (or inability to mount response) with Prevnar or pneumovax remain vulnerable to S. pneumonia infection even if vaccinated on entry, due to delayed kinetics in reaching protective titers. These patients may require prophylactic intervention of hyperimmune Ig with high opsonic titers to S. pneumonia, providing protection until vaccine response elicits protective antibodies. Disclosures All Authors: No reported disclosures

scholarly journals Respiratory viral infections in the elderly

2021 ◽  
Vol 15 ◽  
pp. 175346662199505
Author(s):  
Alastair Watson ◽  
Tom M. A. Wilkinson
Keyword(s):  
Immune System ◽  
Viral Infections ◽  
Point Of Care ◽  
The Elderly ◽  
Respiratory Viruses ◽  
Morbidity And Mortality ◽  
Detection Methods ◽  
Respiratory Viral Infections ◽  
Tract Infections ◽  
Prolonged Hospital

With the global over 60-year-old population predicted to more than double over the next 35 years, caring for this aging population has become a major global healthcare challenge. In 2016 there were over 1 million deaths in >70 year olds due to lower respiratory tract infections; 13–31% of these have been reported to be caused by viruses. Since then, there has been a global COVID-19 pandemic, which has caused over 2.3 million deaths so far; increased age has been shown to be the biggest risk factor for morbidity and mortality. Thus, the burden of respiratory viral infections in the elderly is becoming an increasing unmet clinical need. Particular challenges are faced due to the interplay of a variety of factors including complex multimorbidities, decreased physiological reserve and an aging immune system. Moreover, their atypical presentation of symptoms may lead to delayed necessary care, prescription of additional drugs and prolonged hospital stay. This leads to morbidity and mortality and further nosocomial spread. Clinicians currently have limited access to sensitive detection methods. Furthermore, a lack of effective antiviral treatments means there is little incentive to diagnose and record specific non-COVID-19 viral infections. To meet this unmet clinical need, it is first essential to fully understand the burden of respiratory viruses in the elderly. Doing this through prospective screening research studies for all respiratory viruses will help guide preventative policies and clinical trials for emerging therapeutics. The implementation of multiplex point-of-care diagnostics as a mainstay in all healthcare settings will be essential to understand the burden of respiratory viruses, diagnose patients and monitor outbreaks. The further development of novel targeted vaccinations as well as anti-viral therapeutics and new ways to augment the aging immune system is now also essential. The reviews of this paper are available via the supplemental material section.

scholarly journals The immune landscape of IgA induction in the gut

2021 ◽  
Author(s):  
Claudia Seikrit ◽  
Oliver Pabst
Keyword(s):  
Protective Immunity ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Dark Side ◽  
Secretory Immunoglobulin A ◽  
Antibody Isotype ◽  
Mucosal Antibody ◽  
Key Concepts ◽  
Basic Understanding ◽  
Secretory Immunoglobulin

AbstractAntibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody isotype, protects against infections, shields the mucosal surface from toxins and environmental factors, and regulates immune homeostasis and a peaceful coexistence with our microbiota. However, the dark side of IgA biology promotes the formation of immune complexes and provokes pathologies, e.g., IgA nephropathy (IgAN). The precise mechanisms of how IgA responses become deregulated and pathogenic in IgAN remain unresolved. Yet, as the field of microbiota research moved into the limelight, our basic understanding of IgA biology has been taking a leap forward. Here, we discuss the structure of IgA, the anatomical and cellular foundation of mucosal antibody responses, and current concepts of how we envision the interaction of SIgA and the microbiota. We center on key concepts in the field while taking account of both historic findings and exciting new observations to provide a comprehensive groundwork for the understanding of IgA biology from the perspective of a mucosal immunologist.

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