scholarly journals Acquisition of Maternal Antibodies both from the Placenta and by Lactation Protects Mouse Offspring from Yersinia pestis Challenge

2012 ◽  
Vol 19 (11) ◽  
pp. 1746-1750 ◽  
Author(s):  
Zhizhen Qi ◽  
Haihong Zhao ◽  
Qingwen Zhang ◽  
Yujing Bi ◽  
Lingling Ren ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Subunit Vaccine ◽  
Protective Efficacy ◽  
Passive Immunization ◽  
Maternal Antibodies ◽  
Newborn Mice ◽  
Content Type ◽  
Specific Antibodies ◽  
Transmission Modes ◽  
Passive Antibodies

ABSTRACTArtificially passive immunization has been demonstrated to be effective againstYersinia pestisinfection in animals. However, maternal antibodies' protective efficacy against plague has not yet been demonstrated. Here, we evaluated the kinetics, protective efficacy, and transmission modes of maternal antibodies, using mice immunized with plague subunit vaccine SV1 (20 μg of F1 and 10 μg of rV270). The results showed that the rV270- and F1-specific antibodies could be detected in the sera of newborn mice (NM) until 10 and 14 weeks of age, respectively. There was no antibody titer difference between the parturient mice immunized with SV1 (PM-S) and the caesarean-section newborns (CSN) from the PM-S or between the lactating mice immunized by SV1 (LM-S) and the cross-fostered mice (CFM) during 3 weeks of lactation. The NM had a 72% protection against 4,800 CFUY. pestisstrain 141 challenge at 6 weeks of age, whereas at 14 weeks of age, NM all succumbed to 5,700 CFU ofY. pestischallenge. After 7 weeks of age, CFM had an 84% protection against 5,000 CFU ofY. pestischallenge. These results indicated that maternal antibodies induced by the plague subunit vaccine in mother mice can be transferred to NM by both placenta and lactation. Passive antibodies from the immunized mothers could persist for 3 months and provide early protection for NM. The degree of early protection is dependent on levels of the passively acquired antibody. The results indicate that passive immunization should be an effective countermeasure against plague during its epidemics.

scholarly journals Clearance of Staphylococcus aureus from In Vivo Models of Chronic Infection by Immunization Requires Both Planktonic and Biofilm Antigens

2019 ◽  
Vol 88 (1) ◽  
Author(s):  
Janette M. Harro ◽  
Yvonne Achermann ◽  
Jeffrey A. Freiberg ◽  
Devon L. Allison ◽  
Kristen J. Brao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protective Efficacy ◽  
Passive Immunization ◽  
Quadrivalent Vaccine ◽  
Bacterial Populations ◽  
In Vivo Models ◽  
Content Type ◽  
Pentavalent Vaccine ◽  
And Control

ABSTRACT Staphylococcus aureus is a causative agent of chronic biofilm-associated infections that are recalcitrant to resolution by the immune system or antibiotics. To combat these infections, an antistaphylococcal, biofilm-specific quadrivalent vaccine against an osteomyelitis model in rabbits has previously been developed and shown to be effective at eliminating biofilm-embedded bacterial populations. However, the addition of antibiotics was required to eradicate remaining planktonic populations. In this study, a planktonic upregulated antigen was combined with the quadrivalent vaccine to remove the need for antibiotic therapy. Immunization with this pentavalent vaccine followed by intraperitoneal challenge of BALB/c mice with S. aureus resulted in 16.7% and 91.7% mortality in pentavalent vaccine and control groups, respectively (P < 0.001). Complete bacterial elimination was found in 66.7% of the pentavalent cohort, while only 8.3% of the control animals cleared the infection (P < 0.05). Further protective efficacy was observed in immunized rabbits following intramedullary challenge with S. aureus, where 62.5% of the pentavalent cohort completely cleared the infection, versus none of the control animals (P < 0.05). Passive immunization of BALB/c mice with serum IgG against the vaccine antigens prior to intraperitoneal challenge with S. aureus prevented mortality in 100% of mice and eliminated bacteria in 33.3% of the challenged mice. These results demonstrate that targeting both the planktonic and biofilm stages with the pentavalent vaccine or the IgG elicited by immunization can effectively protect against S. aureus infection.

scholarly journals Passive Immunization Reduces Murine Cytomegalovirus-Induced Brain Pathology in Newborn Mice

2008 ◽  
Vol 82 (24) ◽  
pp. 12172-12180 ◽  
Author(s):  
Đurđica Cekinović ◽  
Mijo Golemac ◽  
Ester Pernjak Pugel ◽  
Jelena Tomac ◽  
Luka Čičin-Šain ◽  
...  
Keyword(s):  
Virus Titer ◽  
Passive Immunization ◽  
Immune Serum ◽  
Murine Cytomegalovirus ◽  
Cns Infection ◽  
Newborn Mice ◽  
Specific Antibodies ◽  
Control Serum ◽  
The Brain ◽  
Infected Newborn

ABSTRACT Human cytomegalovirus (HCMV) is the most frequent cause of congenital viral infections in humans and frequently leads to long-term central nervous system (CNS) abnormalities that include learning disabilities, microcephaly, and hearing loss. The pathogenesis of the CNS infection has not been fully elucidated and may arise as a result of direct damage of CMV-infected neurons or indirectly secondary to inflammatory response to infection. We used a recently established model of mouse CMV (MCMV) infection in newborn mice to analyze the contribution of humoral immunity to virus clearance from the brain. In brains of MCMV-infected newborn mice treated with immune serum, the titer of infectious virus was reduced below detection limit, whereas in the brains of mice receiving control (nonimmune) serum significant amounts of virus were recovered. Moreover, histopathological and immunohistological analyses revealed significantly less CNS inflammation in mice treated with immune serum. Treatment with MCMV-specific monoclonal antibodies also resulted in the reduction of virus titer in the brain. Recipients of control serum or irrelevant antibodies had more viral foci, marked mononuclear cell infiltrates, and prominent glial nodules in their brains than mice treated with immune serum or MCMV-specific antibodies. In conclusion, our data indicate that virus-specific antibodies have a protective role in the development of CNS pathology in MCMV-infected newborn mice, suggesting that antiviral antibodies may be an important component of protective immunological responses during CMV infection of the developing CNS.

scholarly journals Characterization and Protective Efficacy of Type III Secretion Proteins as a Broadly Protective Subunit Vaccine against Salmonella enterica Serotypes

2018 ◽  
Vol 86 (3) ◽  
Author(s):  
Francisco J. Martinez-Becerra ◽  
Prashant Kumar ◽  
Vikalp Vishwakarma ◽  
Jae Hyun Kim ◽  
Olivia Arizmendi ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Subunit Vaccine ◽  
Protective Efficacy ◽  
Spectroscopic Techniques ◽  
Secretion Systems ◽  
Amino Acid Sequence Level ◽  
Lethal Challenge ◽  
Content Type ◽  
Type Iii

ABSTRACT Nontyphoidal Salmonella enterica serotypes (NTS) are the leading cause of hospitalization and death due to foodborne illnesses. NTS are the costliest of the foodborne pathogens and cause ∼$4 billion annually in health care costs. In Africa, new invasive NTS are the leading cause of bacteremia, especially in HIV-positive children and adults. Current vaccines against S. enterica are not broadly protective and most are directed at the typhoid-causing serotypes, not the NTS. All S. enterica strains require two type III secretion systems (T3SS) for virulence. The T3SS needle tip protein and the first translocator are localized to the T3SS needle tip and are required for pathogenesis of S. enterica . Collectively they are 95 to 98% conserved at the amino acid sequence level among all S. enterica strains. The Salmonella pathogenicity island 1 or 2 tip and first translocator proteins were genetically fused to produce the S1 and S2 fusion proteins, respectively, as potential vaccine candidates. S1 and S2 were then characterized using spectroscopic techniques to understand their structural and biophysical properties. Formulated at the proper pH, S1, S2, or S1 plus S2 (S1S2), admixed with adjuvant, was used to immunize mice followed by a lethal challenge with S. enterica serotype Typhimurium or S. enterica serotype Enteritidis. The S1S2 formulation provided the highest protective efficacy, thus demonstrating that an S1S2 subunit vaccine can provide broad, serotype-independent protection, possibly against all S. enterica serotypes. Such a finding would be transformative in improving human health.

scholarly journals Impact of Detergent on Biophysical Properties and Immune Response of the IpaDB Fusion Protein, a Candidate Subunit Vaccine against Shigella Species

2014 ◽  
Vol 83 (1) ◽  
pp. 292-299 ◽  
Author(s):  
Xiaotong Chen ◽  
Shyamal P. Choudhari ◽  
Francisco J. Martinez-Becerra ◽  
Jae Hyun Kim ◽  
Nicholas E. Dickenson ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Subunit Vaccine ◽  
Protective Efficacy ◽  
Recombinant Expression ◽  
Protein A ◽  
Interleukin 17 ◽  
Content Type ◽  
Thermal Plasticity ◽  
Empirical Phase Diagram ◽  
Induced Aggregation

Shigellaspp. are causative agents of bacillary dysentery, a human illness with high global morbidity levels, particularly among elderly and infant populations.Shigellainfects via the fecal-oral route, and its virulence is dependent upon a type III secretion system (T3SS). Two components of the exposed needle tip complex of theShigellaT3SS, invasion plasmid antigen D (IpaD) and IpaB, have been identified as broadly protective antigens in the mouse lethal pneumonia model. A recombinant fusion protein (DB fusion) was created by joining the coding sequences of IpaD and IpaB. The DB fusion is coexpressed with IpaB's cognate chaperone, IpgC, for proper recombinant expression. The chaperone can then be removed by using the mild detergents octyl oligooxyethelene (OPOE) orN,N-dimethyldodecylamineN-oxide (LDAO). The DB fusion in OPOE or LDAO was used for biophysical characterization and subsequent construction of an empirical phase diagram (EPD). The EPD showed that the DB fusion in OPOE is most stable at neutral pH below 55°C. In contrast, the DB fusion in LDAO exhibited remarkable thermal plasticity, since this detergent prevents the loss of secondary and tertiary structures after thermal unfolding at 90°C, as well as preventing thermally induced aggregation. Moreover, the DB fusion in LDAO induced higher interleukin-17 secretion and provided a higher protective efficacy in a mouse challenge model than did the DB fusion in OPOE. These data indicate that LDAO might introduce plasticity to the protein, promoting thermal resilience and enhanced protective efficacy, which may be important in its use as a subunit vaccine.

scholarly journals A Bivalent Typhoid Live Vector Vaccine Expressing both Chromosome- and Plasmid-Encoded Yersinia pestis Antigens Fully Protects against Murine Lethal Pulmonary Plague Infection

2014 ◽  
Vol 83 (1) ◽  
pp. 161-172 ◽  
Author(s):  
James E. Galen ◽  
Jin Yuan Wang ◽  
Jose A. Carrasco ◽  
Scott A. Lloyd ◽  
Gabriela Mellado-Sanchez ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Protective Efficacy ◽  
Serum Antibody ◽  
Antigen Expression ◽  
Effector Proteins ◽  
Great Promise ◽  
Content Type ◽  
Bivalent Vaccine ◽  
Vector Vaccine ◽  
Boost Immunization

Live attenuated bacteria hold great promise as multivalent mucosal vaccines against a variety of pathogens. A major challenge of this approach has been the successful delivery of sufficient amounts of vaccine antigens to adequately prime the immune system without overattenuating the live vaccine. Here we used a live attenuatedSalmonella entericaserovar Typhi strain to create a bivalent mucosal plague vaccine that produces both the protective F1 capsular antigen ofYersinia pestisand the LcrV protein required for secretion of virulence effector proteins. To reduce the metabolic burden associated with the coexpression of F1 and LcrV within the live vector, we balanced expression of both antigens by combining plasmid-based expression of F1 with chromosomal expression of LcrV from three independent loci. The immunogenicity and protective efficacy of this novel vaccine were assessed in mice by using a heterologous prime-boost immunization strategy and compared to those of a conventional strain in which F1 and LcrV were expressed from a single low-copy-number plasmid. The serum antibody responses to lipopolysaccharide (LPS) induced by the optimized bivalent vaccine were indistinguishable from those elicited by the parent strain, suggesting an adequate immunogenic capacity maintained through preservation of bacterial fitness; in contrast, LPS titers were 10-fold lower in mice immunized with the conventional vaccine strain. Importantly, mice receiving the optimized bivalent vaccine were fully protected against lethal pulmonary challenge. These results demonstrate the feasibility of distributing foreign antigen expression across both chromosomal and plasmid locations within a single vaccine organism for induction of protective immunity.

scholarly journals Intranasal Administration of an Inactivated Yersinia pestis Vaccine with Interleukin-12 Generates Protective Immunity against Pneumonic Plague

2011 ◽  
Vol 18 (11) ◽  
pp. 1925-1935 ◽  
Author(s):  
Devender Kumar ◽  
Girish Kirimanjeswara ◽  
Dennis W. Metzger
Keyword(s):  
Yersinia Pestis ◽  
Protective Efficacy ◽  
Bacterial Colonization ◽  
Lethal Dose ◽  
Interleukin 12 ◽  
Cell Vaccine ◽  
Mouse Serum ◽  
Immune Mouse ◽  
Pneumonic Plague ◽  
Content Type

ABSTRACTInhalation ofYersinia pestiscauses pneumonic plague, which rapidly progresses to death. A previously licensed killed whole-cell vaccine is presently unavailable due to its reactogenicity and inconclusive evidence of efficacy. The present study now shows that vaccination intranasally (i.n.) with inactivatedY. pestisCO92 (iYp) adjuvanted with interleukin-12 (IL-12) followed by an i.n. challenge with a lethal dose ofY. pestisCO92 prevented bacterial colonization and protected 100% of mice from pneumonic plague. Survival of the vaccinated mice correlated with levels of systemic and lung antibodies, reduced pulmonary pathology and proinflammatory cytokines, and the presence of lung lymphoid cell aggregates. Protection against pneumonic plague was partially dependent upon Fc receptors and could be transferred to naïve mice with immune mouse serum. On the other hand, protection was not dependent upon complement, and following vaccination, depletion of CD4 and/or CD8 T cells before challenge did not affect survival. In summary, the results demonstrate the safety, immunogenicity, and protective efficacy of i.n. administered iYp plus IL-12 in a mouse model of pneumonic plague.

scholarly journals Protective Efficacy of Monoclonal Antibodies Neutralizing Alpha-Hemolysin and Bicomponent Leukocidins in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Trang T. T. Vu ◽  
Nhu T. Q. Nguyen ◽  
Vuvi G. Tran ◽  
Emmanuelle Gras ◽  
Yanjie Mao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protective Efficacy ◽  
Rabbit Model ◽  
Passive Immunization ◽  
Necrotizing Pneumonia ◽  
Partial Protection ◽  
Content Type ◽  
Alpha Hemolysin ◽  
Wide Range ◽  
Panton Valentine Leukocidin

ABSTRACT Staphylococcus aureus is a major human pathogen that causes a wide range of infections by producing an arsenal of cytotoxins. We found that passive immunization with either a monoclonal antibody (MAb) neutralizing alpha-hemolysin or a broadly cross-reactive MAb neutralizing Panton-Valentine leukocidin, leukocidin ED, and gamma-hemolysins HlgAB and HlgCB conferred only partial protection, whereas the combination of those two MAbs conferred significant protection in a rabbit model of necrotizing pneumonia caused by the USA300 methicillin-resistant S. aureus epidemic clone.

scholarly journals Decline of maternal antibodies to plague in Norway rats

1977 ◽  
Vol 78 (1) ◽  
pp. 27-31
Author(s):  
James E. Williams ◽  
George H. G. Eisenberg ◽  
Dan C. Cavanaugh
Keyword(s):  
Yersinia Pestis ◽  
Rattus Norvegicus ◽  
Passive Immunization ◽  
Active Immunization ◽  
Maternal Antibody ◽  
Maternal Antibodies ◽  
Young Rats ◽  
Fraction I ◽  
Norway Rats

SUMMARYThe decline of maternal antibodies to the fraction I antigen of Yersinia pestis was investigated in newly weaned Rattus norvegicus obtained from dams vaccinated with strain EV76(51f) of Y. pestis. IHA titre decreased by 50% each 7.3 days and CF titre declined 50% each 10.0 days in young rats. An analysis of available data indicated that maternal IHA and CF antibodies could persist to 3 months of age. Therefore, positive serologic reactions in young R. norvegicus, detected in the course of serological surveys, could be the result either of active immunization after exposure to the plague bacillus or of transient passive immunization (i.e. maternal antibody).

scholarly journals Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing

mBio ◽  
2011 ◽  
Vol 2 (5) ◽  
Author(s):  
Masahide Yano ◽  
Shruti Gohil ◽  
J. Robert Coleman ◽  
Catherine Manix ◽  
Liise-anne Pirofski
Keyword(s):  
Monoclonal Antibodies ◽  
Streptococcus Pneumoniae ◽  
Quorum Sensing ◽  
Direct Effect ◽  
Pneumococcal Disease ◽  
Effector Cell ◽  
Capsular Polysaccharide ◽  
Genetic Exchange ◽  
Content Type ◽  
Specific Antibodies

ABSTRACTThe use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two differentStreptococcus pneumoniaeserotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotypeinvitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells.IMPORTANCECurrent thought holds that pneumococcal capsular polysaccharide (PPS)-binding antibodies protect against pneumococcus by inducing effector cell opsonic killing of the homologous serotype. While such antibodies are an important part of how pneumococcal vaccines protect against pneumococcal disease, PPS-specific antibodies that do not exhibit this activity but are highly protective against pneumococcus in mice have been identified. This article examines the effect of nonopsonic PPS-specific monoclonal antibodies (MAbs) on the biology ofStreptococcus pneumoniae. The results showed that in the presence of a competence-stimulating peptide (CSP), such MAbs increase the frequency of pneumococcal transformation. Further studies with one such MAb showed that it altered the expression of genes involved in quorum sensing and increased competence-induced killing or fratricide. These findings reveal a novel, previously unsuspected mechanism by which certain PPS-specific antibodies exert a direct effect on pneumococcal biology that has broad implications for bacterial clearance, genetic exchange, and antibody immunity to pneumococcus.

scholarly journals Effects of Tedizolid Phosphate on Survival Outcomes and Suppression of Production of Staphylococcal Toxins in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Vien T. M. Le ◽  
Hoan N. Le ◽  
Marcos Gabriel Pinheiro ◽  
Kenneth J. Hahn ◽  
Mary L. Dinh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Production ◽  
Protective Efficacy ◽  
Survival Rates ◽  
Rabbit Model ◽  
Rank Test ◽  
Necrotizing Pneumonia ◽  
Time Curve ◽  
Content Type

ABSTRACT The protective efficacy of tedizolid phosphate, a novel oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, and saline in a rabbit model of Staphylococcus aureus necrotizing pneumonia. Tedizolid phosphate was administered to rabbits at 6 mg/kg of body weight intravenously twice daily, which yielded values of the 24-h area under the concentration-time curve approximating those found in humans. The overall survival rate was 83% for rabbits treated with 6 mg/kg tedizolid phosphate twice daily and 83% for those treated with 50 mg/kg linezolid thrice daily (P = 0.66 by the log-rank test versus the results obtained with tedizolid phosphate). These survival rates were significantly greater than the survival rates of 17% for rabbits treated with 30 mg/kg vancomycin twice daily (P = 0.003) and 17% for rabbits treated with saline (P = 0.002). The bacterial count in the lungs of rabbits treated with tedizolid phosphate was significantly decreased compared to that in the lungs of rabbits treated with saline, although it was not significantly different from that in the lungs of rabbits treated with vancomycin or linezolid. The in vivo bacterial production of alpha-toxin and Panton-Valentine leukocidin, two key S. aureus-secreted toxins that play critical roles in the pathogenesis of necrotizing pneumonia, in the lungs of rabbits treated with tedizolid phosphate and linezolid was significantly inhibited compared to that in the lungs of rabbits treated with vancomycin or saline. Taken together, these results indicate that tedizolid phosphate is superior to vancomycin for the treatment of S. aureus necrotizing pneumonia because it inhibits the bacterial production of lung-damaging toxins at the site of infection.

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