scholarly journals Göttingen Minipigs as a Model to Evaluate Longevity, Functionality, and Memory of Immune Response Induced by Pertussis Vaccines

2021 ◽  
Vol 12 ◽  
Author(s):  
Céline Vaure ◽  
Véronique Grégoire-Barou ◽  
Virginie Courtois ◽  
Emilie Chautard ◽  
Cyril Dégletagne ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Vaccine Development ◽  
Vaccination Schedule ◽  
Memory B Cells ◽  
Immune Memory ◽  
Preclinical Model ◽  
Göttingen Minipig ◽  
Cellular Immune

Evaluation of the short-term and long-term immunological responses in a preclinical model that simulates the targeted age population with a relevant vaccination schedule is essential for human vaccine development. A Göttingen minipig model was assessed, using pertussis vaccines, to demonstrate that vaccine antigen-specific humoral and cellular responses, including IgG titers, functional antibodies, Th polarization and memory B cells can be assessed in a longitudinal study. A vaccination schedule of priming with a whole cell (DTwP) or an acellular (DTaP) pertussis vaccine was applied in neonatal and infant minipigs followed by boosting with a Tdap acellular vaccine. Single cell RNAsequencing was used to explore the long-term maintenance of immune memory cells and their functionality for the first time in this animal model. DTaP but not DTwP vaccination induced pertussis toxin (PT) neutralizing antibodies. The cellular immune response was also characterized by a distinct Th polarization, with a Th-2-biased response for DTaP and a Th-1/Th-17-biased response for DTwP. No difference in the maintenance of pertussis-specific memory B cells was observed in DTaP- or DTwP-primed animals 6 months post Tdap boost. However, an increase in pertussis-specific T cells was still observed in DTaP primed minipigs, together with up-regulation of genes involved in antigen presentation and interferon pathways. Overall, the minipig model reproduced the humoral and cellular immune responses induced in humans by DTwP vs. DTaP priming, followed by Tdap boosting. Our data suggest that the Göttingen minipig is an attractive preclinical model to predict the long-term immunogenicity of human vaccines against Bordetella pertussis and potentially also vaccines against other pathogens.

Comparable Long-Term Persistence of Anti-FVIII Antibodies in Hemophilic E17 Mice on Different Genetic Backgrounds Despite Significant Differences in the Amplitude of the Immune Responses.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1027-1027
Author(s):  
Natalie Bauer ◽  
Christina Hausl ◽  
Rafi U. Ahmad ◽  
Bernhard Baumgartner ◽  
Hans Peter Schwarz ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Genetic Background ◽  
Neutralizing Antibodies ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Mouse Strains ◽  
Igg Antibodies ◽  
Specific Memory

Abstract About 30% of patients with severe hemophilia A develop neutralizing antibodies against FVIII (FVIII inhibitors) following replacement therapy. The type of FVIII gene mutation as well as other predisposing genetic factors contribute to the inhibitor phenotype. Based on these findings, we asked if the genetic background modulates the long-term persistence of anti-FVIII antibodies and anti-FVIII antibody secreting plasma cells in the E17 murine hemophilia model. Furthermore, we asked if the recently described inhibition of memory-B-cell re-stimulation by high doses of FVIII is influenced by the genetic background of the murine model. E17 mice on two different genetic backgrounds (C57Bl/6J and Balb/c) were treated with four doses of 200 ng human FVIII at weekly intervals. Anti-FVIII antibodies and anti-FVIII antibody secreting plasma cells were followed up to 12 months after the last dose of FVIII. Antibody titers and subclasses of antibodies (IgM, IgG1, IgG2a, IgG2b, IgG3) were measured by ELISA. Antibody secreting plasma cells in spleen and bone marrow were detected by ELISPOT as described (Hausl et al., Thromb Haemost 2002). The re-stimulation of FVIII-specific memory B cells was studied as described recently (Hausl et al., Blood 2005). Anti-FVIII antibodies and anti-FVIII antibody secreting plasma cells were first detectable in E17 Balb/c mice. IgM antibodies in the circulation and IgM secreting plasma cells in the spleen were observed after the first dose of FVIII, IgG antibodies and IgG secreting plasma cells after the second dose. No anti-FVIII antibodies after the first dose of FVIII were observed in E17 C57BL/6J mice but both IgM and IgG antibodies as well as IgM and IgG producing plasma cells were detectable after the second dose of FVIII. The antibody response involved all IgG subclasses in both mouse strains. However, IgG1 was dominant in E17 Balb/c mice whereas IgG2a was dominant in E17 C57BL/6J mice. When the in vitro restimulation of FVIII-specific memory B cells was examined, similar patterns were observed for both mouse strains. Low concentrations of FVIII between 10 and 100 ng/ml FVIII restimulated memory B cells and induced their differentiation into antibody secreting plasma cells whereas high concentrations of FVIII between 1,000 and 20,000 ng/ml FVIII inhibited memory-B-cell-restimulation. These results indicate that the dose-dependent effect of FVIII on the restimulation of FVIII-specific memory B cells does not depend on the genetic background. The major difference between both hemophilic mouse strains was the amplitude of the anti-FVIII immune response. Peak titers of anti-FVIII antibodies and peak concentrations of anti-FVIII antibody secreting plasma cells in spleen and bone marrow were significantly higher in E17 C57BL/6J mice than in E17 Balb/c mice. Whether or not higher ELISA titers correlate with higher Bethesda titers of neutralizing antibodies is currently being investigated. Despite the substantial differences in the amplitude of the immune response, anti-FVIII antibodies and anti-FVIII antibody secreting plasma cells persisted for the whole observation period of 12 months after the last dose of FVIII in both mouse strains. We conclude that the amplitude of the anti-FVIII immune response in hemophilic mice is significantly different between E17 C57BL/6J and E17 Balb/c mice. However, the persistence of the immune response is comparable.

scholarly journals Memory immune response: a major challenge in vaccination

2012 ◽  
Vol 3 (5) ◽  
pp. 479-486 ◽  
Author(s):  
Antonella Prisco ◽  
Piergiuseppe De Berardinis
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Vaccine Development ◽  
Immune Memory ◽  
Gene Expression Signatures ◽  
Antibody Titers ◽  
Memory Immune Response ◽  
Protective Threshold

AbstractA crucial challenge for vaccine development is to design vaccines that induce a long-lasting protective immune response, i.e., immune memory. The persistence of antigen-specific antibody titers over a protective threshold, and the ability to exibit a ‘recall response’ to a subsequent encounter with an antigen have long been the only measurable correlates of vaccine take and immune memory development, suffering from the disadvantage of relying on long-term monitoring of the immune response. In the last few years, advances in the technologies for the identification and characterization of the cell subsets and molecular pathways involved in the immune response to vaccination have allowed innovative approaches to the identification of early correlates of immune memory. In this review, we discuss recent data and hypotheses on early correlates of the development of immune memory, with special emphasis on the gene expression signatures that underlie the self-renewal ability of some lymphocyte subsets, and their similarities with gene expression signatures in stem cells.

scholarly journals mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern

2021 ◽  
Author(s):  
Rishi R Goel ◽  
Mark M Painter ◽  
Sokratis A Apostolidis ◽  
Divij Mathew ◽  
Wenzhao Meng ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Immune Memory ◽  
Severe Illness ◽  
Post Vaccination ◽  
Cell Responses ◽  
Cellular Immune

SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naive and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and current variants of concern for at least 6 months after mRNA vaccination. Finally, we observed that boosting of pre-existing immunity with mRNA vaccination in SARS-CoV-2 recovered individuals primarily increased antibody responses in the short-term without significantly altering antibody decay rates or long-term B and T cell memory. Together, this study provides insights into the generation and evolution of vaccine-induced immunity to SARS-CoV-2, including variants of concern, and has implications for future booster strategies.

scholarly journals Comparable Long-Term Rabies Immunity in Foxes after IntraMuscular and Oral Application Using a Third-Generation Oral Rabies Virus Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 49
Author(s):  
Verena te Kamp ◽  
Virginia Friedrichs ◽  
Conrad M. Freuling ◽  
Ad Vos ◽  
Madlin Potratz ◽  
...  
Keyword(s):  
Immune Response ◽  
Rabies Virus ◽  
Specific Binding ◽  
Lethal Dose ◽  
Genetically Engineered ◽  
Routes Of Administration ◽  
Safety Studies ◽  
Oral Rabies Vaccine ◽  
Cellular Immune

The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre- and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

scholarly journals Antigen-Specific B Cell Memory

2000 ◽  
Vol 191 (7) ◽  
pp. 1149-1166 ◽  
Author(s):  
Louise J. McHeyzer-Williams ◽  
Melinda Cool ◽  
Michael G. McHeyzer-Williams
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Cell Memory ◽  
Specific Memory ◽  
B Cell Memory ◽  
Cellular Components

The mechanisms that regulate B cell memory and the rapid recall response to antigen remain poorly defined. This study focuses on the rapid expression of B cell memory upon antigen recall in vivo, and the replenishment of quiescent B cell memory that follows. Based on expression of CD138 and B220, we reveal a unique and major subtype of antigen-specific memory B cells (B220−CD138−) that are distinct from antibody-secreting B cells (B220+/−CD138+) and B220+CD138− memory B cells. These nonsecreting somatically mutated B220− memory responders rapidly dominate the splenic response and comprise >95% of antigen-specific memory B cells that migrate to the bone marrow. By day 42 after recall, the predominant quiescent memory B cell population in the spleen (75–85%) and the bone marrow (>95%) expresses the B220− phenotype. Upon adoptive transfer, B220− memory B cells proliferate to a lesser degree but produce greater amounts of antibody than their B220+ counterparts. The pattern of cellular differentiation after transfer indicates that B220− memory B cells act as stable self-replenishing intermediates that arise from B220+ memory B cells and produce antibody-secreting cells on rechallenge with antigen. Cell surface phenotype and Ig isotype expression divide the B220− compartment into two main subsets with distinct patterns of integrin and coreceptor expression. Thus, we identify new cellular components of B cell memory and propose a model for long-term protective immunity that is regulated by a complex balance of committed memory B cells with subspecialized immune function.

The Two-years Immune Effect Between 0-1-2-months and 0-1-6-months of HBV Vaccination Schedule in Adults

2021 ◽  
Author(s):  
Juan Wang ◽  
Chang-Hai Liu ◽  
Yuanji Ma ◽  
Xia Zhu ◽  
Liru Luo ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Adult Population ◽  
Compliance Rate ◽  
Vaccination Schedule ◽  
Completion Rate ◽  
Immune Memory ◽  
Short Term ◽  
Immune Effect ◽  
Hbv Vaccination

Abstract Background: The short-term 0-1-2-months hepatitis B virus (HBV) vaccination schedule was previously proposed in the adult population; however, its long-term immune effect remains unclear. The present study was aimed to investigate 1) the 2-months and 2-year immune effect of HBV vaccination; and 2) compliance rate between 0-1-2-months and 0-1-6-months vaccination schedules in adults.Method: A total of 1281 subjects tested for HBsAg(-) and Hepatitis B surface antibody (anti-HBs)(-) were recruited. Participants from two distant counties were inoculated hepatitis B yeast vaccine for 10ug per dose each time, with 0-1-2-months (n=606) and 0-1-6-months (n=675) vaccination schedule, sequentially followed-up at two months and two years after the 3rd injection.Results: There was no statistical difference in anti-HBs seroconversion rate between 0-1-2-months and 0-1-6-months vaccination schedule at two months (91.96% vs 89.42%, p=0.229) and two years (81.06% vs. 77.14%, p=0.217). Quantitative anti-HBs level of 0-1-2-months vaccination schedule was not different with 0-1-6-months vaccination schedule at 2 months (anti-HBs1) (342.12 ± 378.42 m IU/ml vs. 392.38 ± 391.96 m IU/ml, p=0.062), but was higher at two years (anti-HBs2) (198.37 ± 286.44 m IU /ml vs. 155.65 ± 271.73 m IU /ml, p=0.048). By subgroup analysis, 0-1-2-months vaccination schedule showed better maintenance (p=0.041) and delayed reinforcement (p=0.019) in comparison to 0-1-6 vaccination schedule. The 0-1-2-months vaccination schedule also increased the 3rd-time injection completion rate (89.49% vs. 84.49%, p=0.010).Conclusion: the 0-1-2-months vaccination could obtain a similar short-term immune effect, but achieve a better long-term immune memory and a higher completion rate in the adult population.Trial registration: None

scholarly journals The Cellular Immune Response to Rabies Vaccination: A Systematic Review

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 110 ◽  
Author(s):  
Overduin ◽  
van Dongen ◽  
Visser
Keyword(s):  
Immune Response ◽  
Cellular Immune Response ◽  
Plasma Cells ◽  
Primary Response ◽  
Extensive Literature ◽  
Registration Number ◽  
Extensive Literature Search ◽  
Cellular Immune ◽  
Rabies Vaccination

The effectiveness of rabies vaccines is conventionally determined by serological testing. In addition to this assessment of humoral immunity, cellular immunity could help assess effectiveness and protection through a broad range of parameters. Therefore, this study aimed to systematically review all literature on the kinetics and composition of the cellular immune response to rabies vaccination in humans. A total of 1360 studies were identified in an extensive literature search. Twenty studies were selected for inclusion. In a primary response, plasma cells are detectable from day 7 to day 14, peaking at day 10. Memory B-cells appear from day 10 up to at least day 28. After revaccination, natural killer (NK) cells are the first detectable cellular parameters. Further research is required to assess cellular parameters in relation to long-term (serological) immunity. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42019134416.

Long-term presence of memory B-cells specific for different vaccine components

Vaccine ◽  
2009 ◽  
Vol 28 (1) ◽  
pp. 179-186 ◽  
Author(s):  
A.M. Buisman ◽  
C.G.H. de Rond ◽  
K. Öztürk ◽  
H.I. ten Hulscher ◽  
R.S. van Binnendijk
Keyword(s):  
B Cells ◽  
Memory B Cells
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