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Immunologic memory induced by a glycoconjugate vaccine in a murine adoptive lymphocyte transfer model.

We have developed an adoptive cell transfer model in mice to study the ability of a glycoprotein conjugate vaccine to induce immunologic memory for the polysaccharide moiety. We used type III capsular polysaccharide from the clinically relevant pathogen group B streptococci conjugated to tetanus toxoid (GBSIII-TT) as our model vaccine. GBS are a major cause of neonatal infections in humans, and type-specific antibodies to the capsular polysaccharide protect against invasive disease. Adoptive transfer of splenocytes from mice immunized with the GBSIII-TT conjugate vaccine conferred anti-polysaccharide immunologic memory to naive recipient mice. The transfer of memory occurred in a dose-dependent manner. The observed anamnestic immune response was characterized by (i) more rapid kinetics, (ii) isotype switching from immunoglobulin M (IgM) to IgG, and (iii) 10-fold-higher levels of type III-specific IgG antibody than for the primary response in animals with cells transferred from placebo-immunized mice. The adoptive cell transfer model described in this paper can be used for at least two purposes: (i) to evaluate conjugate vaccines with different physicochemical properties for their ability to induce immunologic memory and (ii) to study the cellular interactions required for an immune response to these molecules.

Adoptive Transfer↗

In vitro studies on the immunological memory for antibody response to bovine serum albumin.

Immunological memory for T and B cells was studied in an in vitro culture system with spleen cells from mice primed with bovine serum albumin (BSA). Spleen cells taken from mice immunized at various times previously with a single intravenous injection of alum-precipitated (AP) BSA and bacterial endotoxin (ET) were cultured in Marbrook's system with dinitrophenylated (DNP) BSA as the in vitro antigen. In the cultures of spleen cells obtained from mice primed more than 14 days previously an IgG-predominant anti-BSA response was generated. However, no anti-BSA response was observed in the culture of spleen cells taken from mice primed 7 days previously (day 7 spleen cells). The failure of day 7 spleen cells to generate an antibody response in vitro was shown to be attributable to both the lack of B memory cells and the effect of "suppressive" macrophages induced by ET. On the other hand, anti-BSA memory in the spleen of mice primed with AP-BSA plus ET and 2 months later challenged with AP-BSA matured within 7 days and declined rather quickly by 30 days after the challenge. The difference in the time course of the generation of memory between the spleen cells from primary and from secondary immunized mice might be attributable to the difference in the maturation of memory B cells, since the time course of the development of memory T cells after the secondard immunization was similar to that observed after primary immunization.

Animals↗

Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure.

AIMS: To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory. METHODS: Unmatched case-control study in the UK and Eire 1992-2001 and Victoria, Australia 1988-1990. A total of 93 children were identified as having invasive Hib disease following three doses of conjugate vaccine in infancy through post licensure surveillance throughout the UK and Eire; 92 unvaccinated children admitted to an Australian paediatric hospital with invasive Hib disease were used as historical controls. Convalescent serum was taken for measurement of Hib antibody concentration, and clinical information relating to potential disease risk factors was collected. The geometric mean concentrations of convalescent Hib antibodies were compared between immunised and unimmunised children, using raw and adjusted data. RESULTS: Hib conjugate vaccine immunised children had higher serum Hib antibody responses to disease (geometric mean concentration (GMC) 10.81 microg/ml (95% CI 6.62 to 17.66) than unimmunised children (1.06 microg/ml (0.61 to 1.84)) (p < 0.0001). However, following adjustment for the significant confounding influences of age at presentation and timing of serum collection, a difference persisted only in children presenting with meningitis (vaccinated GMC 3.78 microg/ml (2.78 to 5.15); unvaccinated GMC 1.48 microg/ml (0.90 to 2.21); p = 0.003). CONCLUSIONS: Higher antibody responses to invasive Hib disease in vaccinated children with meningitis reflect priming for immunologic memory by the vaccine. Although a majority of children in the UK are protected from Hib disease by immunisation, the relative roles of immunologic memory and other immune mechanisms in conferring protection remain unclear.

Age Factors↗

Immunological memory after immunization with oral cholera B subunit--whole-cell vaccine in Swedish volunteers.

The capacity of peroral immunization with either two or three doses of B subunit-whole cell (B-WC) cholera vaccine to induce immunological memory was examined in Swedish volunteers by testing the immune responses to a single dose of B-WC vaccine given 10 months after the initial immunization. Antibody responses in serum and antibody-secreting cell (ASC) responses in peripheral blood were studied, since these responses seem to reflect the gut mucosal IgA immune responses after oral immunization with B-WC vaccine. Previously immunized volunteers responded to a single dose of B-WC vaccine more frequently and with higher levels of IgA and IgG antitoxin antibodies as well as vibriocidal antibodies in serum than did previously unvaccinated controls. The IgA-ASC responses to cholera toxin B subunit were also higher in primed volunteers than in controls. Two doses of B-WC vaccine were as effective as three doses in inducing immunological memory for cholera immunity. A new B-WC cholera vaccine based on recombinant B subunit had the same capacity as the first generation of B-WC vaccine to induce immunological memory for cholera antitoxin immunity.

Administration, Oral↗

Durable immunity and immunologic memory to a parasite antigen induced by somatic transgene immunization.

Somatic transgene immunization (STI) is an alternative approach to immunization mediated by inoculation of plasmid DNA. In the experiments presented here we show that inoculation of plasmid DNA carrying an immunoglobulin heavy chain gene under the control of tissue-specific regulatory elements, leads to immunity and persistent immunologic memory against a peptide epitope encoded in the third complementarity-determining region. The epitope consists in three repeats of the tetrapeptide Asn-Ala-Asn-Pro (NANP) and is the immunodominant B cell epitope expressed at the surface of Plasmodium falciparum malaria parasite. When inoculated directly in the spleen the plasmid DNA initiated a specific anti-NANP response which lasted for 2 years. During the initial phase of priming the anti-NANP response was higher than that induced by immunization with recombinant protein in immunologic adjuvants. The establishment of immunologic memory was probed by single booster injection at various times after priming. We found that STI induces persistent immunologic memory up to 2 years. The immunologic characteristics of this new model are examined with respect to the requirement for the induction of B cell memory.

Animals↗

[Stimulation of cellular immunity and immunologic memory be somatotropic hormone].

The role of somatotropic hormone (STH) in the development of delayed hypersensitivity and immunological memory was studied in guinea pigs. The STH injected at periods of sensitization and realization of delayed hypersensitivity stimulated the skin reactions. Suppression of the endogenic STH by the antiserum to the guinea pig. STH prevented development of hypersensitivity at both periods. Hypersensitivity was restored after the cessation of antiserum effects. The period of sensitization proved to be most sensitive, whereas the period of immunological memory persistence remained resistant.

Animals↗

Immunity and immunological memory following smallpox vaccination.

The smallpox vaccine consists of live vaccinia virus and is generally considered the gold standard of vaccines, since it is the only one that has led to the complete eradication of an infectious disease from the human population. Renewed fears that smallpox might be deliberately released in an act of bioterrorism have led to resurgence in the study of immunity and immunological memory to vaccinia virus and other poxviruses. Here we review our current understanding of memory T-cell, memory B-cell, and antibody responses to vaccinia and related poxviruses, both in animal models and human subjects. Of particular interest are recent advances in understanding protective immunity to poxviruses, quantifying immunological memory to the smallpox vaccine in humans, and identifying major vaccinia-specific T-cell and B-cell epitopes. In addition, potential mechanisms for maintenance of immunological memory are discussed.

Animals↗

[Patterns of the forming of an immunologic memory to staphylococcal corpuscular antigen].

The experiments carried out on inbred mice have revealed that the level of the immunological memory to staphylococci depends on the intensity of the antigenic stimulation; high priming dose of antigen proving to be the most effective one. The opposite character of immune responsiveness observed during primary antibody response to particulate staphylococcal antigen in C3H and A/Sn mice increased after the second immunization. It is established that immunological memory to staphylococci may be induced in genetically athymic mice. Many antibody-forming cells are found in the bone marrow of the secondary immunized mice. This phenomenon may be due to the repopulation of the bone marrow tissue by recirculating memory cells.

Agglutinins↗

Stability of a diverse immunological memory is determined by T cell population dynamics.

The correlation between properties of the T cell memory pool and the two regulatory mechanisms of cell death (apoptosis) and memory entry (differentiation) is investigated mathematically. Apoptosis of T cells occurs at the end of an immune response, removing unwanted activated T cells. T cells escaping apoptosis enter the memory pool composed of T cells specific for previously encountered antigens. We find that the relative efficiencies of these two pathways determine the clonal distribution and the long-term stability of the memory pool by regulating the number of new entries. The main result presented in this paper is that immunological memory of previously encountered pathogens cannot be erased by either severe or repeat infections with a particular pathogen (the diversity of the memory pool is ensured) only if apoptosis and/or memory differentiation are regulated by population dependent processes. Furthermore, vaccination properties are improved significantly by population dependent mechanisms and our mathematical analysis reveals that the T cell population must communicate with other parts of the immune system to ensure optimal performance of immunological memory.

Apoptosis↗

An experimental study on the endurance of immunologic memory of intradermal micro-injection with rabies vaccine and boosting immune effect.

The purpose of the experimental study is to observe the effect of the immune recall responses induced by intramuscular (i.m.) injection with concentrated Primary Hamster Kidney Cell Vaccine(PHKCV) on days 180, 365, 545 and 730 after 0.1 mL nonconcentrated PHKCV was inoculated intradermally (i.d.), so as to determine the duration of the immunologic memory induced by i.d. 0.1 mL nonconcentrated PHKCV and chieve the goal of protecting the rabies patients with a short incubation. The results indicated that there were four intervals of 180, 365, 545 and 730 days between i.d. and i.d. PHKCV, the seroconversion rates being respectively 96.55%, 100%, 100%(180 day); 76.67%, 100%, 100%(365 day); 75.86%, 100%, 100%(545 day) and 75.00%, 100%, 100%(730 day) on days 7, 14 and 30 after the first dose i.m., the seroconversion rates of four experimental groups were all markedly higher than that of five routine doses (40.74%) (P < 0.01) on days 7 after the first dose i.m. The immune endurance of concentrated PHKCV and the enhancing immune effect of the vaccine following booster injection 365 days later were also observed. The results indicated that the seroconversion rates on days 180, 365 and 380 (on day 15 after boosting injection) were 96%, 83.33% and 100% respectively. The stated results prove that the concentrated PHKCV has better immune endurance and the immunologic memory induced by i.d. 0.1 mL nonconcentrated PHKCV can maintain two years. The immune effect inoculated by i.m. two or three doses on day 730 after i.d. 0.1 mL nonconcentrated PHKCV was better than that of five routine doses as the first time vaccination. If intradermal micro-injection were performed with higher titre of rabies vaccines, the longer time of immunologic memory would be maintained.

Adolescent↗

Amplification of cell-associated immunological memory by secondary antigenic stimulus. Secondary type increase in memory.

In mice primed with a mixture of bovine serum albumin (BSA) and adjuvant (capsular polysaccharide of Klebsiella pneumoniae (CPS-K)) cell-associated immunological memory was increased secondarily after a second injection of BSA alone, whereas a primary injection of BSA alone into normal unprimed mice did not result in detectable memory. The optimum antigen doses for expression of the primary and secondary memories of adoptively transferred cells from unboosted primed donors or boosted donors in in vivo culture systems were very similar, although those observed in intact mice were very different, as reported previously. The size of the secondary memory of adoptively transferred cells from boosted donors was more than ten times greater than that of the primary memory of adoptively transferred cells from unboosted primed donors. The lag period for increase of the secondary memory was shorter than that for the primary memory. Both primary and secondary memories increased during a long period (up to 3 months) after the antigenic stimulus. From the results of this study it was concluded that cell-associated immunological memory could be amplified in a secondary fashion upon contact with a second stimulus.

Adjuvants, Immunologic↗

Immunogenicity and immunologic memory of meningococcal C conjugate vaccine in premature infants.

BACKGROUND: Protein-polysaccharide conjugate vaccines against Neisseria meningitidis serogroup C were introduced into the U.K. routine immunization schedule in 1999. This study is the first to describe both persistence of antibody and evidence for induction of immune memory using meningococcal C conjugate (MCC) vaccine in preterm infants. METHODS: Immunogenicity and induction of immunologic memory by as MCC vaccine was assessed in premature infants; 62 preterm and 60 term controls received MCC at the accelerated schedule (2, 3 and 4 months of age). A meningococcal C polysaccharide challenge was administered at 12 months of age. RESULTS: Both groups achieved similar protective titers after primary immunization that then waned significantly by 1 year of age. Postchallenge serum bactericidal activity was significantly lower in preterm infants (P = 0.03); 73% of preterm versus 88% of term controls achieved a 4-fold rise in serum bactericidal activity (P = 0.07). CONCLUSIONS: MCC vaccine is immunogenic and primes for immunologic memory in preterm infants. The decreased memory responses in these preterm infants in conjunction with waning clinical efficacy data for all U.K. infants suggest a role for a routine booster dose of vaccine in all infants receiving MCC, especially those born preterm.

Antibodies, Bacterial↗

Ability of spleen cells from tumor bearing mice to transfer immunologic memory.

The ability of splenocytes from tumorous mice to transfer immunologic memory was tested. Three syngeneic experimental tumors from highly inbred strains were used; fibrosarcoma, lymphoma and Lewis lung carcinoma. Splenocytes from tumorous mice were collected after rejection of allogeneic skin which had been grafted at different stages of the tumor disease, and injected into lethally irradiated syngeneic recipients. These secondary hosts were grafted with the same allogeneic skin graft as their donors and the ability of cells transplanted from tumorous donors to transfer memory to allograft was tested. Tumorous mice seemed to have more memory cells (T lymphocytes) in their spleens than the controls.

Animals↗

Characterization of immunological memory cells. A minireview.

This paper reviews the information concerning immunological memory T and B cells. It shows that the existence of different or a single lineage of memory and naive cells is still a question. The recirculation pattern of memory cells is different from naive cells. A unique recirculation for memory T or B cells is suggested while the bcl2 gene expression possibly plays role in the longevity of memory cells. Various phenotypic markers are demonstrated only on memory or on naive cells; however, a reliable and convenient method for the detection of memory cells still needs to be explored.

Animals↗

Cells participating in immunologic memory induced with RNA from the spleens of immunized mice.

Ribonucleic acid (immune RNA, iRNA) extracted from the spleens of mice immunized with heterologous red blood cells induced antigen-specific immunologic memory. The type of cells (T cells, B cells) which participate in immunologic memory induced with iRNA was investigated. Immune RNA-primed T cells cooperated with normal, iRNA-primed or antigen-primed B cells and induced a high IgM response. Immune RNA-primed B cells did not cooperate with normal T cells, but did with iRNA- or antigen-primed T cells. The activities of iRNA-primed T and B cells were antigen-specific.

Animals↗

Immunologic "memory" for microbial antigens in lymphocytes obtained from human bronchial mucosa.

Memory for previous immunologic contact with microbial antigens has been detected in lymphocytes from human bronchi as a secondary immune response, when tested in vitro. Antigens stimulated a predominantly proliferative response in blood lymphocytes that was significantly greater than the response in mucosal lymphocytes with purified protein derivative and Herpes simplex type 1 antigens. Co-culture experiments with autologous blood lymphocytes showed that cell-dependent suppression was one mechanism of the low response of bronchial lymphocytes. In the patient who inhaled a foreign body, a proliferative response to antigens was restricted to bronchus-associated lymphoid tissue lymphocytes, suggesting a recruitment of antigen-reactive cells from a circulating pool.

Antigens, Viral↗

Immunologic memory 5 years after meningococcal A/C conjugate vaccination in infancy.

Infant vaccination with meningococcal conjugates may provide long-term protection against disease. Antibody levels and immunologic memory were assessed in 5-year-old Gambian children who received meningococcal A/C conjugate vaccination (MenA/C) in infancy. At 2 years, they were randomized to receive a booster of MenA/C (conjugate group), meningococcal A/C polysaccharide (MPS group), or inactivated polio vaccine (IPV group). All groups were revaccinated with 10 microg MPS at 5 years of age, as were 39 previously unvaccinated age-matched control subjects. Before revaccination, titers were higher in the conjugate and MPS groups than in control subjects (P<.001); titers for the IPV group were similar to those for control subjects. Ten days after revaccination, the conjugate and IPV groups had similar serogroup C serum bactericidal antibody titers (3421 vs. 2790, respectively). These levels were significantly higher than those in the MPS (426) and control (485) groups (P<.001). Thus, immunologic memory was sustained for > or =5 years; however, MPS challenge at 2 years interfered with a subsequent memory response.

Adult↗

Influence of suspension on the expression of protective immunological memory to murine Listeria monocytogenes infection.

Female BDF1 mice were immunized with virulent Listeria monocytogenes, which resulted in the generation of a long-lived state of protective immunological memory for this facultative intracellular bacterial pathogen. The influence of antiorthostatic suspension, a ground-based model employed to simulate certain aspects of weightlessness that occur during spaceflight, on the capacity of these mice to express memory immunity was evaluated. Memory-immune mice were suspended by the tail in the orthostatic or antiorthostatic position and were reinfected with a lethal dose of virulent L. monocytogenes. It was found that suspension did not influence the kinetics of bacterial growth in vivo when the rechallenge infection was started concurrently with the suspension. However, mice that were reinfected on day 2 or 4 of the suspension exhibited an enhanced capacity to eliminate the infection. Attenuation of this enhancing effect was observed when mice were infected on day 7 of the suspension. These results indicate that the stress of antiorthostatic suspension can influence the capacity of the murine host to express protective immunological memory to pathogenic bacteria.

Animals↗