scholarly journals Intranasal Immunization with Pneumococcal Conjugate Vaccines with LT-K63, a Nontoxic Mutant of Heat-Labile Enterotoxin, as Adjuvant Rapidly Induces Protective Immunity against Lethal Pneumococcal Infections in Neonatal Mice

2002 ◽  
Vol 70 (3) ◽  
pp. 1443-1452 ◽  
Author(s):  
Håvard Jakobsen ◽  
Stefania Bjarnarson ◽  
Giuseppe Del Giudice ◽  
Monique Moreau ◽  
Claire-Anne Siegrist ◽  
...  
Keyword(s):  
Early Life ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Antibody Responses ◽  
Mucosal Immunization ◽  
Pneumococcal Infections ◽  
Conjugate Vaccines ◽  
Pneumococcal Conjugate Vaccines ◽  
Serotype 1 ◽  
Specific Igg

ABSTRACT Immunization with pneumococcal polysaccharides (PPS) conjugated to tetanus toxoid (TT) (Pnc-TT) elicits protective immunity in an adult murine pneumococcal infection model. To assess immunogenicity and protective immunity in early life, neonatal (1 week old) and infant (3 weeks old) mice were immunized intranasally (i.n.) or subcutaneously (s.c.) with Pnc-TT of serotype 1 (Pnc1-TT). Anti-PPS-1 and anti-TT immunoglobulin G (IgG) and IgM antibodies were measured in serum and saliva, and vaccine-induced protection was evaluated by i.n. challenge with serotype 1 pneumococci. Pnc1-TT was immunogenic in neonatal and infant mice when administered s.c. without adjuvant: a majority of the young mice were protected from bacteremia and a reduction of pneumococcal density in the lungs was observed, although antibody responses and protective efficacy remained lower than in adults. The addition of LT-K63, a nontoxic mutant of heat-labile enterotoxin, as adjuvant significantly enhanced PPS-1-specific IgG responses and protective efficacy following either s.c. or i.n. Pnc1-TT immunization. Mucosal immunization was particularly efficient in neonates, as a single i.n. dose of Pnc1-TT and LT-K63 induced significantly higher PPS-1-specific IgG responses than s.c. immunization and was sufficient to protect neonatal mice against pneumococcal infections, whereas two s.c. doses were required to induce complete protection. In addition, i.n. immunization with Pnc1-TT and LT-K63 induced a vigorous salivary IgA response. This suggests that mucosal immunization with pneumococcal conjugate vaccines and LT-K63 may be able to circumvent some of the limitations of neonatal antibody responses, which are required for protective immunity in early life.

scholarly journals Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 989
Author(s):  
Hae-Ji Kang ◽  
Ki-Back Chu ◽  
Min-Ju Kim ◽  
Hyunwoo Park ◽  
Hui Jin ◽  
...  
Keyword(s):  
B Cells ◽  
Toxoplasma Gondii ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Antibody Responses ◽  
Strongly Correlated ◽  
Cpg Odn ◽  
Virus Like Particle ◽  
Iga Antibody ◽  
Specific Igg

Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles (VLPs) after challenge infection with T. gondii (ME49) in mice (BALB/c) upon one, two, and three immunizations. Immunization with adjuvanted T. gondii VLPs induced higher levels of T. gondii-specific IgG and/or IgA antibody responses, germinal center (GC) B cells, total B cells, and CD4+ and CD8+ T cells compared with unadjuvanted VLPs. Increasing the number of immunizations was strongly correlated with enhanced protective immunity against T. gondii in mice, with the highest protection being demonstrated in mice thrice-immunized with either adjuvanted T. gondii VLPs or VLPs alone. Notably, lesser bodyweight reductions and cerebral cyst counts were observed in mice receiving multiple immunizations with the adjuvanted VLPs, thereby confirming the effectiveness of adjuvanted boost immunizations. These results demonstrated that multiple immunizations with T. gondii VLPs is an effective approach, and the CpG-ODN can be developed as an effective adjuvant for T. gondii VLP vaccines.

scholarly journals Pneumococcal Conjugate Vaccines Overcome Splenic Dependency of Antibody Response to Pneumococcal Polysaccharides

2001 ◽  
Vol 69 (12) ◽  
pp. 7583-7587 ◽  
Author(s):  
Mijke A. Breukels ◽  
Andre Zandvoort ◽  
Germie P. J. M. van den Dobbelsteen ◽  
Adrie van den Muijsenberg ◽  
Monique E. Lodewijk ◽  
...  
Keyword(s):  
Antibody Response ◽  
Conjugate Vaccine ◽  
Primary Response ◽  
Antibody Responses ◽  
Capsular Polysaccharides ◽  
Pneumococcal Infections ◽  
Conjugate Vaccines ◽  
Pneumococcal Conjugate Vaccines ◽  
Increased Risk ◽  
Pneumococcal Polysaccharides

ABSTRACT Protection against infections with Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides that facilitate phagocytosis. Asplenic patients are at increased risk for pneumococcal infections, since both phagocytosis and the initiation of the antibody response to polysaccharides take place in the spleen. Therefore, vaccination with pneumococcal polysaccharide vaccines is recommended prior to splenectomy, which, as in the case of trauma, is not always feasible. We show that in rats, vaccination with a pneumococcal conjugate vaccine can induce good antibody responses even after splenectomy, particularly after a second dose. The spleen remains necessary for a fast, primary response to (blood-borne) polysaccharides, even when they are presented in a conjugated form. Coadministration of a conjugate vaccine with additional nonconjugated polysaccharides of other serotypes did not improve the response to the nonconjugated polysaccharides. We conclude that pneumococcal conjugate vaccines can be of value in protecting asplenic or hyposplenic patients against pneumococcal infections.

scholarly journals Kinetics and Avidity of Antibodies Evoked by Heptavalent Pneumococcal Conjugate Vaccines PncCRM and PncOMPC in the Finnish Otitis Media Vaccine Trial

2005 ◽  
Vol 73 (1) ◽  
pp. 369-377 ◽  
Author(s):  
Nina Ekström ◽  
Heidi Åhman ◽  
Jouko Verho ◽  
Jukka Jokinen ◽  
Merja Väkeväinen ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Vaccine Trial ◽  
Antibody Responses ◽  
Conjugate Vaccines ◽  
Pneumococcal Conjugate Vaccines ◽  
Correlates Of Protection ◽  
The Mean ◽  
Antibody Kinetics ◽  
Kinetics Of

ABSTRACT The licensure of new pneumococcal conjugate vaccines (PCVs) relies on immunogenicity data. When defining correlates of protection, vaccine efficacy data must be included. In the FinOM Vaccine Efficacy Trial, the PncOMPC vaccine showed an efficacy profile similar to that of the licensed PncCRM vaccine despite different antibody responses after primary and booster vaccinations. We determined antibody kinetics and avidities in a subgroup of infants participating in the FinOM trial. A total of 166 infants in three vaccine groups were immunized at 2, 4, 6, and 12 months of age with 7-valent PCV, PncCRM or PncOMPC, or hepatitis B vaccine. Concentrations of serum immunoglobulin G (IgG) against pneumococcal capsular polysaccharides were determined at 2, 4, 6, 7, 12, 13, and 24 months of age, and the avidity index (AI) to serotypes 6B, 19F, and 23F were determined at 7, 12, 13, and 24 months of age by enzyme immunoassay. Both PCVs were highly immunogenic, but they demonstrated different kinetics of antibody response; the concentration of IgG against serotypes 6B, 19F, and 23F declined faster after the third and fourth doses of vaccine in the PncCRM group than in the PncOMPC group. For both PCVs, the mean AI of anti-6B and -23F, but not of anti-19F, increased during the follow-up, which is in line with serotype-specific protection in the FinOM trial. Our data suggest that the kinetics and avidities of antibodies should be considered, in addition to antibody responses, when defining correlates of protection.

scholarly journals Intranasal Immunization with Pneumococcal Polysaccharide Conjugate Vaccines Protects Mice against Invasive Pneumococcal Infections

1999 ◽  
Vol 67 (8) ◽  
pp. 4128-4133 ◽  
Author(s):  
Håvard Jakobsen ◽  
Eiríkur Saeland ◽  
Sveinbjörn Gizurarson ◽  
Dominique Schulz ◽  
Ingileif Jónsdóttir
Keyword(s):  
Lethal Dose ◽  
Immunoglobulin A ◽  
Respiratory Pathogen ◽  
Protein Antigens ◽  
Pneumococcal Infections ◽  
Conjugate Vaccines ◽  
Mucosal Vaccination ◽  
Serum Igg ◽  
Serotype 1 ◽  
Subcutaneous Immunization

ABSTRACT Host defenses against Streptococcus pneumoniae depend largely on opsonophagocytosis mediated by antibodies and complement. Since pneumococcus is a respiratory pathogen, mucosal immune responses may play a significant role in the defense against pneumococcal infections. Thus, mucosal vaccination may be an alternative approach to current immunization strategies, but effective adjuvants are required. Protein antigens induce significant mucosal immunoglobulin A (IgA) and systemic IgG responses when administered intranasally (i.n.) with the glyceride-polysorbate based adjuvant RhinoVax (RV) both in experimental animals and humans. The immunogenicity and efficacy of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 was studied in mice after i.n. immunization with RV. Antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA) and compared to antibody titers induced by parenteral immunization. The PNCs induced significant systemic IgG and IgA antibodies after i.n. immunization only when given with RV and, for serotype 1, serum IgG titers were comparable to titers induced by subcutaneous immunization. In addition, i.n. immunization with PNC-1 in RV elicited detectable mucosal IgA. These results demonstrate that RV is a potent mucosal adjuvant for polysaccharides conjugated to proteins. A majority of the PNC-1-immunized mice were protected against both bacteremia and pneumonia after i.n. challenge with a lethal dose of serotype 1 pneumococci, and protection correlated significantly with the serum IgG titers. Similarly, the survival of mice immunized i.n. with PNC-3 in RV was significantly prolonged. These results indicate that mucosal vaccination with PNC and adjuvants may be an alternative strategy for prevention against pneumococcal infections.

Immunization of mice against Trichinella spiralis and T. britovi using excretory and secretory antigens

1997 ◽  
Vol 71 (2) ◽  
pp. 109-112 ◽  
Author(s):  
P.K. Goyal ◽  
F. Bolas-Fernandez ◽  
D. Wakelin
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Trichinella Spiralis ◽  
Antibody Responses ◽  
Current Understanding ◽  
T Helper ◽  
T Helper 2 ◽  
Mesenteric Node ◽  
Specific Igg

AbstractImmune responses to immunization and infection with Trichinella spiralis and T. britovi were studied in NIH high-responder mice. Overall it was shown that T. britovi was the more immunogenic, immunization and challenge with this species giving greater host-protective immunity. This greater immunogenicity was reflected in higher proliferative responses when mesenteric node lymphocytes (MLNC) from immunized mice were restimulated with T. britovi antigens in vitro and in higher levels of T helper 2 (Th2) lymphocyte-dependent specific IgG1 antibody responses against this species. MLNC from mice immunized against T. britovi released more IL-5 when restimulated in vitro, again suggesting a greater T helper 2 subset response, but after infection the highest levels of IL-5 were recorded from MLNC taken from T. spiralis challenged mice. These data are discussed in relation to current understanding of immunological differences between species and isolates of the genus Trichinella.

scholarly journals Impact of Pre-Existing Immunity on Live Attenuated Influenza Vaccine-Induced Cross-Protective Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 459 ◽  
Author(s):  
Sreeja Roy ◽  
Clare M Williams ◽  
Julian Pardo ◽  
Danushka K Wijesundara ◽  
Yoichi Furuya
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Cellular Immunity ◽  
Specific Antibody ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Cross Protection ◽  
Antibody Responses ◽  
Live Attenuated Influenza Vaccine ◽  
Heterologous Challenge

The efficacy of the intranasally (i.n.) delivered live attenuated influenza vaccine (LAIV) is variable and, in some seasons, suboptimal. In this study, we report that LAIV exhibits cross-protective efficacy in mice, potentially associated with cellular immunity as opposed to antigen-specific antibody responses. However, pre-exposure to the intramuscularly (i.m.) delivered inactivated influenza vaccine (IIV) severely impaired LAIV-induced cross-protection against heterologous challenge, potentially by inhibiting replication of LAIV. Our findings suggest that pre-existing immunity afforded by IIV suppresses cross-protective T cell immunogenicity of LAIV.

scholarly journals Recombinant Group B Streptococcus Beta C Protein and a Variant with the Deletion of Its Immunoglobulin A-Binding Site Are Protective Mouse Maternal Vaccines and Effective Carriers in Conjugate Vaccines

2007 ◽  
Vol 75 (7) ◽  
pp. 3455-3461 ◽  
Author(s):  
Hsiao-Hui Yang ◽  
Lawrence C. Madoff ◽  
Hilde-Kari Guttormsen ◽  
Yong-Dong Liu ◽  
Lawrence C. Paoletti
Keyword(s):  
Binding Site ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Group B Streptococcus ◽  
Immunoglobulin A ◽  
Capsular Polysaccharides ◽  
C Protein ◽  
Conjugate Vaccines ◽  
Group B ◽  
Effective Carrier

ABSTRACT Immunogenic vaccines against group B Streptococcus (GBS) have been created by coupling the GBS capsular polysaccharides (CPS) to carrier proteins. The GBS beta C protein (BCP) serves as an effective carrier while inducing protective immunity against BCP-expressing strains. BCP also binds human immunoglobulin A (IgA), a characteristic that may be undesirable for use in humans. Here, we examined the immunogenicity and protective efficacy of a recombinant GBS BCP (rBCP), an rBCP modified to eliminate its IgA-binding site (rBCPΔIgA), and their corresponding GBS serotype III CPS conjugates (III-rBCP and III-rBCPΔIgA). Deletion of the IgA-binding site or conjugation to CPS did not alter antigenic BCP epitopes. Recombinant proteins and conjugates elicited specific, high-titered IgG in mice. Antisera to rBCP, rBCPΔIgA, III-rBCP, and III-rBCPΔIgA opsonized GBS strains A909 (Ia/BCP+) and H36B (Ib/BCP+) for killing by HL-60 cells; antiserum to III-rBCP and III-rBCPΔIgA also opsonized strain M781 (III/BCP−). Vaccination of female mice with either rBCP or rBCPΔIgA protected ∼40% of their pups challenged with GBS strain A909. Pups born to III-rBCP- or III-rBCPΔIgA-vaccinated dams survived at rates of 56% and 66%, respectively. Over 90% of pups born to dams that received the type III CPS conjugates survived challenge with GBS strain M781. In summary, rBCP and rBCPΔIgA proteins and the conjugates containing them were immunogenic in mice, inducing both CPS- and protein-specific functional IgG. These results suggest that the rBCPΔIgA could be used as a carrier to augment the immunogenicity of the CPS while expanding coverage to GBS strains bearing BCP.

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