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gammadelta cells and the regulation of mucosal immune responses.

We are only now uncovering the potentially important contributions made to immune responses by gammadelta cells. These contributions are likely to be particularly important at mucosal sites, where gammadelta cells are disproportionately enriched. Indeed, gammadelta cells have proven biological activity in the lung. In addition, gammadelta cells are also enriched in young rather than adult animals. Studies of mutant mice have demonstrated that alphabeta T cells are seemingly essential for high-affinity, cognate immunological memory, whereas gammadelta cells contribute to the early stages of an immune response and to the regulation of alphabeta T cell- and B cell-mediated immunity. To explore further the role of gammadelta cells in immune responses, we have investigated whether their contribution is greater during the early period of life, when the cells are more abundant. In a natural system of coccidial infection of gut epithelial cells, we find that alphabeta T cell responses are less essential for immunoprotection during primary challenge of young mice than is true for adult animals. This "ineffectiveness" creates a "window of importance" for the immunoprotective capacity of gammadelta cells, which seem thereby to be more crucial in young compared with older animals. The relative ineffectiveness of alphabeta T cells in young mice may be attributable to a bias toward Th2 activity. We therefore hypothesize that gammadelta cell activity, elicited by infection early in life, may compensate for defects in Th1 activity and may actually accelerate the bias in alphabeta T cells away from Th2. This has obvious implications for susceptibility to Th2-type allergic responses.

Adult↗

Germinal centre destruction as a major pathway of HIV pathogenesis.

Human immunodeficiency virus (HIV)-induced destruction of follicular dendritic cells (FDCs), which are important in immunological memory, may be a major pathway of HIV pathogenesis. We use a mathematical model to investigate this hypothesis and conclude that a low level of FDC destruction could ultimately result in loss of control of HIV. Their slow turnover makes them good candidates for the part of the immune system that fails during the long period of HIV infection. As FDC destruction is essentially a misdirected immune response, too much immunotherapy may be detrimental. Our model shows how to estimate this critical level of immunotherapy. We derive an expression for the time taken to the loss of immune control. Transient changes in the viral growth rate before the immune system fails do not affect this time, providing a possible explanation for the results of the Concorde trial. We suggest that inducible B cell function is a good potential marker of disease progression, indicating the functional ability of the FDC network. Finally, we rereview data in the light of the FDC theory, paying particular attention to data on CD4+ numbers and function that are inconsistent with the classical view of HIV pathogenesis.

Antigen-Presenting Cells↗

Innate immunity and biodefence vaccines.

Host defence in vertebrates is achieved by the integration of two distinct arms of the immune system: the innate and adaptive responses. The innate response acts early after infection (within minutes), detecting and responding to broad cues from invading pathogens. The adaptive response takes time (days to weeks) to become effective, but provides the fine antigenic specificity required for complete elimination of the pathogen and the generation of immunologic memory. Antigen-independent recognition of pathogens by the innate immune system leads to the rapid mobilization of immune effector and regulatory mechanisms that provide the host with three critical advantages: (i) initiating the immune response (both innate and adaptive) and providing the inflammatory and co-stimulatory context for antigen recognition; (ii) mounting a first line of defence, thereby holding the pathogen in check during the maturation of the adaptive response; and (iii) steering the adaptive immune system towards the cellular or humoral responses most effective against the particular infectious agent. The quest for safer and more effective vaccines and immune-based therapies has taken on a sudden urgency with the increased threat of bioterrorism. Only a handful of vaccines covering a small proportion of potential biowarfare agents are available for human use (e.g. anthrax and small pox) and these suffer from poor safety profiles. Therefore, next generation biodefence-related vaccines and therapies with improved safety and the capacity to induce more rapid, more potent and broader protection are needed. To this end, strategies to target both the innate and adaptive immune systems will be required.

Animals↗

Mechanisms of specific immunological unresponsiveness to bacterial lipopolysaccharides.

Low-dose priming of mice with Escherichia coli O113 lipopolysaccharide (LPS) results in the development of immunological memory, whereas low-dose priming with E. coli O55 LPS or Serratia marcescens LPS induces significant antigen-specific unresponsiveness. All three preparations of LPS induced proliferation of mouse splenocytes with similar time course and [3H]thymidine uptake. There was no correlation between the small amounts of serum antibody detected by enzyme-linked immunosorbent assay after low-dose priming and the subsequent generation of either memory or unresponsiveness. Further, the passive transfer of small amounts of LPS-specific antibody had no significant effect on the magnitude of the plaque-forming cell (PFC) response elicited after subsequent immunization. Reduction of the PFC response to E. coli O55 LPS occurred after low-dose priming of nu/nu (as well as nu/+) mice; however, unresponsiveness could not be generated in nu/nu mice by low-dose priming with S. marcescens LPS. Thus, although the development of low-dose unresponsiveness to S. marcescens LPS appears to involve T cells, the response of E. coli O55 LPS does not. Enhancement of the primary PFC response to S. marcescens LPS could be transferred with low-dose primed spleen cells depleted of Lyt-2+ T cells; this suggests that the magnitude of the PFC response to this preparation of LPS is negatively influenced by Lyt-2+ T cells and positively influenced by Lyt-2- spleen cells (i.e., L3T4+ T cells). These findings indicate that T cells appear to be involved in regulating the magnitude of the antibody response to some types of bacterial LPS.

Animals↗

Trypanosoma cruzi: protective response of vaccinated mice is mediated by CD8+ cells, prevents signs of polyclonal T lymphocyte activation, and allows restoration of a resting immune state after challenge.

Currently, there is no vaccine available against Chagas' disease. Immune abnormalities induced by T. cruzi pose particular difficulties for vaccine development, since immunological memory must be able to overcome them to prevent spread of infection/sequelae. We have previously demonstrated that experimental vaccination with live CL-14 trypomastigotes does not induce polyclonal lymphocyte activation, immunosuppression, or pathology and efficiently immunizes against virulent T. cruzi. Herein we show that: (1) expansion of CD4+ and CD8+ subsets peaks 2 weeks after infective challenge in both challenged-vaccinated mice and infected controls, but the former exhibit a smaller increase in blastogenesis and in the numbers of activated CD11a(hi)CD4+ and CD11a(hi)CD8+ cells; (2) in long-term-vaccinated mice, expansion of activated subsets (CD62Llo/- and CD11a(hi)) is accelerated among CD8+ PBL 1 week after challenge; (3) challenged-vaccinated mice retract the CD8+-activated subset 5 weeks after challenge, different from infected controls; (4) protection conferred by CL-14 immunization can be adoptively transferred to naïve recipients with lymphocyte suspensions, and prior depletion of CD8+ (but not of CD4+) cells abolishes protective immunity. Our findings indicate that protective immunity generated by CL-14 immunization involves a transient CD8+ recall response and is capable of preventing the signs of polyclonal lymphocyte activation induced by virulent challenge.

Adoptive Transfer↗

Ribonucleic acid in the immune response.

In the studies of experimental salmonellosis, immunization of mice with a live vaccine SER of S. enteritidis was found to be effective against further infection with virulent S. enteritidis 116--54. Macrophages obtained from the peritoneal cavity, subcutaneous tissue or liver of immunized mice inhibited intracellular growth of bacteria and resisted cell degeneration caused by engulfment of virulent 116--54 bacteria. This immunity was called cellular immunity. We discovered by chance in 1961 a transfer agent of immunity (TA) from the culture fluid of immunized macrophages. This agent is RNA in nature and can be extracted from the spleen, peritoneal exudate cells or the lymph node of immunized animals and is called immune (i) RNA. We could demonstrate antibody activity in macrophages treated in vitro or in vivo with iRNA by the immune adherence hemagglutination technique. Cellulr immunity against tumor cells could be transferred in vitro or in vivo to lymphocytes through iRNA prepared from the spleen cells of syngeneic, allogeneic and xenogeneic animals immunized with the tumor cells. We prepared iRNA against antigens capable of inducing humoral antibody production in animals, i.e., RBCs, bacterial toxin, bacterial flagella and hapten-protein conjugates. Serum antibody was not demonstrated in recipient animals of iRNA's by single or repeated injections of these agents. However, in these animals an increase in the number of specific antibody-carrying cells was found as rosette-formers. It was found further that prior injection of iRNA could induce immunologic memory and produced a high titer of humoral antibody after a boosting stimulation with a small dose of the corresponding antigen. The required interval between the first iRNA and the second antigenic stimulation, and the minimal effective doses of iRNA and antigen are described. We studied the interaction of iRNA with either T- or B-cells and with both cells using adoptive transfer system, athymic nude mice and neonatally thymectomized (NT) mice. Immune rna's against T-dependent and T-independent antigens could not induce the proliferation of antibody-carrying cells in cyclophosphamide-treated (B-cell depleted) mice. But these agents could induce the proliferation of rosette-formers, implying that iRNA's can replace some role of T-cells even against T dependent antigens. B-cells can be directly activated by treatment with iRNA against both T-dependent and T-independnet antigens, and they differentiated into rosette-formers. Passive transfers of iRNA were successful in establishing immunity against infection with S. enteritidis, or immunity to Salmonella flagella, RBCs and hapten-protein conjugates. The ability of iRNA to confer a secondary response of antibody formation is serially and passively transmissible in recipient animals. These facts suggest the presence of some mechanism that is responsible for the amplification of antigenic stimulation in the immune response...

Animals↗

Reciprocal age-related patterns of allergen-specific T-cell immunity in normal vs. atopic infants.

By adulthood there is almost universal immunological memory to aeroallergens, and the presence of allergic disease appears to be related to the nature of the underlying T-helper (Th) cell cytokine responses. The hypothesis of this study is that adult patterns of allergen specific Th-cell memory (Th-2 polarized in atopics vs. Th1 in non-atopics) can be determined in early infancy. Mononuclear cell cytokine responses to house-dust mite were measured at 6-monthly intervals from birth to 2 years of age, using ELISA (IL-10, IL-13, IFN-gamma) and sqRT/PCR (IL-4, IL-5, IL-9, IFN-gamma) in normal infants (n = 14) with no family history or allergic symptoms, and infants with a family history and definite atopy by 2 years (n = 16). Both normals and atopics showed low-level Th2 skewed allergen-specific responses at birth with little accompanying IFN-gamma. The Th2 responses to house-dust mite were higher in normal newborns, who then show a rapid downregulation of these responses in the first year of life. Atopic infants instead show a consolidation of their neonatal patterns of Th2 polarized allergen specific immunity. Earlier studies indicate that neonates at high risk of atopy display diminished capacity for production of the Th1 cytokine IFN-gamma. The present study suggests for the first time that neonates who subsequently develop atopy also initially have reduced capacity to mount Th2 responses. However, in contrast to non-atopics who selectively downregulate their fetal Th2 polarized allergen-specific responses, atopic children display age-associated upregulation of Th2 immunity.

Aging↗

Humoral recall responses in HIV infection. Levels, specificity, and affinity of antigen-specific IgG.

To evaluate the integrity of humoral immunologic memory among persons with HIV infection, we measured the levels, specificity, and functional affinity of circulating antibodies to vaccine-related recall Ag, tetanus (TT) and diphtheria toxoids (DT), and to naturally acquired measles virus, in sera from 17 HIV-seronegative control subjects, 17 asymptomatic HIV-seropositive patients, and 10 patients with AIDS. Preimmunization levels of TT- and measles-specific IgG were similar in all groups, although DT-specific IgG was lower in AIDS patients. Four wk after immunization with TT3 and DT, all groups showed significantly increased specific antibody levels (p less than 0.02). The asymptomatic HIV+ patients and control subjects achieved similar peak serum levels of TT-specific IgG (102 +/- 32 and 169 +/- 36 micrograms/ml, respectively). In contrast, the AIDS patients had lower peak values of both TT- and DT- specific IgG (p less than 0.05). Peak levels correlated directly with the number of CD4+ T cells (p less than 0.05). However, 80 to 100% of all participants tested, independent of HIV status, showed higher levels of TT- and DT-specific IgG 6 mo after immunization compared with preimmunization levels. The antitoxoid antibodies were specific as they did not cross-react with other Ag in competitive inhibition experiments. In addition, all groups exhibited antibodies to TT and DT both pre- and postimmunization of equivalent functional affinity (avidity) (Kd = 10(-10)-10(-11) mol/liter). We conclude that, in contrast to the profoundly depressed humoral responses to new Ag, persons with asymptomatic HIV infection retain humoral immunity to certain recall Ag. These levels of specific IgG to three recall Ag are not proportional to elevated levels of total serum IgG in HIV-infected patients. In addition, many patients with HIV respond to challenge with recall Ag by producing significant amounts of high affinity IgG that may persist over time.

Antibody Affinity↗

Kinetics and drug sensitivity of the anti-hapten and anti-carrier IgG1 and IgG2 antibody production in guinea pigs.

The influence of the hapten-protein ratio on the induction and kinetics of specific IgG1 and IgG2 anti-hapten and anti-carrier antibody synthesis, and the sensitivity of these reactions to cyclophosphamide (CY) and 6-mercaptopurine (6-MP), were studied following immunization with two different dinitrophenylated bovine gamma-globulin (DNP20-BGG and DNP47-BGG) conjugates in Freund's complete adjuvant (FCA) and drug treatment over the first 7 days after antigen injection. The DNP- and BGG-specific IgG1 and IgG2 serum antibody concentrations were determined weekly. Treatment by CY resulted in a complete suppression of the primary IgG1 and IgG2 anti-BGG antibody response, both in the DNP20-BGG and DNP47-BGG immunized guinea pigs. The anti-DNP response was completely suppressed only up to day 14 (DNP20-BGG immunized group) or day 21. This was followed by an increase that was significantly greater in the DNP20-BGG than in the DNP47-BGG immunized animals. The secondary IgG1 anti-BGG immune response induced by an injection of 1 mg BGG on day 86, was uninfluenced in animals immunized with DNP20-BGG but stimulated in the other group treated with DNP47-BGG. The IgG2 was completely suppressed in both groups. 6-MP, known to be less immunosuppressive in guinea pigs, led to very similar results. The finding that in animals immunized with DNP47-BGG the primary anti-BGG IgG2 antibody synthesis was uninfluenced by 6-MP, but the development of a memory was suppressed, would suggest that the primary antibody response and immunological memory are either separate mechanisms or have different sensitivities to 6-MP.

Animals↗

Avoiding deceptive imprinting of the immune response to HIV-1 infection in vaccine development.

Lymphocyte clonal restriction is caused by priming the immune system with an antigen and has been referred to infectious disease study as "original antigenic sin" (OAS), described first for influenza by Francis. OAS is a dominant feature of a normal immune response. Benefits of OAS come from the initial contact with the pathogen, which induces immunological memory. Memory is achieved by priming B and T cells of an immunologically naïve host, and confers protection against infection with the antigen-related pathogen. Thus, a restricted antibody response to viral or parasite antigens is not per se pathogenic. However, the interplay between a "locked-in" immune response and the high genetic variation of the pathogenic agent can result in a deception of the immune system. In the following, clonal restriction of the immune response to HIV is described by giving examples of restricted anti-HIV antibody formation in maternally infected children. Clonal restriction results in host resistance of infected individuals to emerging HIV variants and quasispecies. The problems of classical approaches of vaccine design in AIDS and the lack of protection in vaccinated patients is reviewed.

AIDS Vaccines↗

[Effect of 17beta-estradiol-3-monobenzoate on humoral antibody formation in mice].

17beta-Estradiol-3-monobenzoate injected s.c. in mice led to a dose-dependent stimulation of the global reticuloendothelial clearance function. Furthermore, a significant depression of serum hemagglutinin levels, being independent of the anitgen dose, was noticed. Although a slight decrease of antigen-sensitive (memory) cells was revealed, estradiol treatment before priming failed to impair immunological memory as assayed by hemagglutinin titers in the secondary reaction. Estradiol administration was followed by charakteristic organ weight changes (liver, thymus, adrenals). According to the literature it is suggested that estradiol, like diethylstilbestrol, is capable of depressing humoral antibody formation by differential effects on the reticuloendothelial system.

Adrenal Glands↗

Cancer vaccines: an old idea comes of age.

Cancer vaccines are at the forefront of novel, targeted approaches to cancer treatment. Low toxicity, the potential for circumventing drug cross-resistance, and the potential for persistence of the antitumor effect due to immunologic memory represent a mandate for accelerated clinical development. Advances in molecular immunology have suggested approaches for overcoming the formidable mechanisms of immune tolerance that are pre-established in cancer patients, and many have already been tested in preclinical models. Also, early studies revealed that not all tumor antigens are created equal, and identifying those capable of eliciting immune-mediated tumor rejection is essential to the development of effective recombinant cancer vaccines. While early trials have generally resulted in disappointing clinical outcomes, they have yielded insight into the critical parameters for the design of cancer vaccine trials and provided powerful reagents for tumor antigen identification. By utilizing the lessons learned from the research laboratory and these early clinical trials, informative second generation vaccine trials should have a high likelihood of success. Clinical protocols that consider how best to incorporate therapeutic cancer vaccines into the current standard of care should allow cancer vaccines to take their place alongside traditional cancer treatment modalities in oncology practice.

Animals↗

Defence mechanisms and immune evasion in the interplay between the humane immune system and Plasmodium falciparum.

Immunity to P. falciparum malaria is developed as a result of long term exposure to the parasite and depends on immunological memory. The key directors in immune recognition and regulation of the immunological responses are the T-cells. It seems reasonable to propose that immunity is acquired when a critical mass of T-cells, recognizing relevant malaria antigens, has been developed. These T-cells mediate immunity by regulating macrophage and B-cell activity, but they may also act directly as cytotoxic cells on infected hepatocytes and through production of parasite-toxic cytokines. The potential immune effector mechanisms against P. falciparum are many. The relative importance of each in protection is unknown and protection seems to be mediated through different mechanisms according to the degree of exposure to malaria and the pattern of malaria transmission. Since immunity to malaria is not an absolute phenomenon, many effector mechanisms are probably working together in (partially) protected individuals. Immunity to P. falciparum is acquired after years of exposure to the parasite and several disease episodes. The protracted course to clinical immunity indicates that the parasite interfere with development of immunity. Several mechanisms seem to be operating. 1) Induction of the immune response to some macromolecules is avoided because the parasites are living inside host cells during part of their life cycle, and the reaction to other molecules is apparently avoided by mimicry of host molecules. 2) Immune recognition is hampered by the extraordinary diversity of antigen phenotypes in the parasite population. 3) Immune regulation is obstructed by immune suppression. During P. falciparum malaria such suppression is characterized by a profoundly diminished in vitro proliferative response to malaria antigens, which probably is precipitated by defects in the early events of T-cell activation and inhibition of IL-2 function elucidated, but soluble factors secreted either by the parasites, or by host cells as a result of exposure to the parasite, seem to be involved. 4) Immune effector mechanisms in the liver and the spleen are avoided by sequestration of the mature parasites to the vascular endothelium. The interplay between the human defence system and the malaria parasite governs the symptomatology, the pathology and the development of immunity to the disease. These interactions are extremely complex, and only partly understood. Figure 1 summarizes my view on how these interactions could explain the characteristics of acquired immunity to P. falciparum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Treatment of murine gliomas by adoptive transfer of ex vivo activated tumor-draining lymph node cells.

The adoptive transfer of tumor-reactive T lymphocytes has recently been demonstrated to be an effective means for mediating the regression of experimental intracranial fibrosarcomas. In this study, mice bearing syngeneic intracranial GL261 gliomas were cured by the combination of sublethal whole body irradiation followed by the intravenous transfer of tumor-draining lymph node (LN) T cells activated with anti-CD3 or staphylococcal enterotoxin C2 (SEC2). To further identify the functional effector T cel population in the adoptive immunotherapy, LN T cells were separated into two subsets, based on the level of expression of the cell adhesion molecule CD62L (L-selectin). As few as 5 x 10(5) CD62Llow cells could cure the majority of animals, whereas 2 x 10(6) CD62Lhigh cells were completely ineffective. Moreover, T cells isolated from advanced intracranial tumors were identified to be predominantly CD62Llow. In contrast, spleens contained a mixture of CD62L low and high cells similar to the transferred cell population. T cells in the glioma site were more actively proliferating than those isolated from the spleen. Mice cured of GL261 tumors demonstrated long-term immunologic memory by rejecting intracranial challenges of the original tumor but not an immunologically distinct tumor. Furthermore, despite infiltration of transferred cells into the intracranial tumors, cured mice did not exhibit any apparent neurologic abnormalities during treatment, prolonged follow-up, or after intracranial tumor rechallenge. This study demonstrates the effective treatment of an intracranial murine glioma by the systemic adoptive transfer of activated tumor-draining LN T cells and selective tumor infiltration by the therapeutically active CD62Llow T cells.

Adoptive Transfer↗

Gene expression after vaccination of mice with formulations of diphtheria toxoid or tetanus toxoid and different adjuvants: identification of shared and vaccine-specific genes in spleen lymphocytes.

We immunized mice with four different combinations of diphtheria toxoid or tetanus toxoid with aluminum phosphate or Freund's adjuvant and studied the resulting gene expression profiles in spleen lymphocytes. Genes, which are unique for each combination or shared in several combinations, were found activated, with functions in immune response but also in other cellular processes like apoptosis or signal transduction. Using bioinformatic tools we show, that some of the genes may serve as indicators for adverse reactions, while other genes may be new immune response markers. The results also suggest that adjuvant participates in the formation of an immunological memory.

Adjuvants, Immunologic↗

Human immunodeficiency virus type 1 challenge of chimpanzees immunized with recombinant envelope glycoprotein gp120.

The major envelope glycoprotein, gp120, of human immunodeficiency virus type 1 (HIV-1) was purified from a Chinese hamster ovary cell line transfected with a truncated form of the HIV-1 env gene. The recombinant glycoprotein (rgp120) was formulated with aluminum hydroxide adjuvant and was used to immunize chimpanzees. The recombinant preparation was effective in eliciting cellular and humoral immunity as well as immunologic memory. Anti-rgp 120 antibodies reacted with authentic viral gp120 in immunological blot assays and were able to neutralize HIV-1 infectivity in vitro. Sera from the rgp120-immunized animals were able to neutralize HIV-1 pseudotypes of vesicular stomatitis virus prepared from the IIIB isolate, from which the gene encoding rgp120 was derived, as well as two heterologous isolates, ARV-2 and RF. The immune response elicited against the rgp120 was not effective in preventing viral infection after intravenous challenge with HIV-1. The implications of these results on HIV-1 vaccine development are discussed.

Acquired Immunodeficiency Syndrome↗

The effect of antigenic competition on various manifestations of humoral antibody formation and cellular immunity.

The effect of antigenic competition on various parameters of humoral antibody formation and cellular immunity was studied in mice. Several pairs of antigens were employed in the investigation of the competitive aspects of induction of humoral antibody formation. Induction of a primary immune response to hemocyanin in Swiss white female mice moderately suppressed the induction of both 19S and 7S antibody formation to goose or rat erythrocytes. Suppression of 7S antibody formation was maximal when a time interval of 1-3 days separated the sequence of injections, although suppression was noted for intervals of up to 14 days. The induction of a primary immune response to rat RBC, the second of the two antigens in sequence, also suppressed The induction of both 19S and 7S antibody formation to goose RBC when appropriate intervals of 1-3 days were employed between injections. The induction of a secondary immune response to rat RBC totally suppressed the primary induction of both 19S and 7S antibody formation to goose RBC administered in the appropriate time sequence. Subsequently, it was shown that the secondary immune response to the suppressed antigen (goose RBC) elicited 30 days after induction of a primary immune response (5 days after secondary immunization with rat RBC) was characterized by deficient 19S and 7S antibody production. These levels were suppressed even in comparison with a normal primary immune response to this antigen. The results were interpreted in part on the basis of a deficiency of formation of primed cells associated with immunological memory. Alternatively, evidence was obtained for the development of a split type of immunological tolerance in 6 of 10 animals studied, since a total suppression of 7S antibody production was obtained in association with deficient 19S antibody synthesis (titers < 1/10). The induction of a primary immune response to several antigens in A/J female mice suppressed the processes of cellular immunity as manifested by prolonged survival of skin grafts from C57 BL/6J female donors. These results were interpreted as evidence for the existence and utilization of processing cells by the initial immune stimulus yielding a deficiency of cells available for processing the second antigen administered in sequence.

Animals↗

Primary and booster mucosal immune responses to meningococcal group A and C conjugate and polysaccharide vaccines administered to university students in the United Kingdom.

Meningococcal group A+C capsular polysaccharide (PS) conjugate vaccines may prime for serum immunoglobulin G (IgG) memory responses to meningococcal capsular PS. It is not known whether these vaccines induce immunological memory at the mucosal level, which may be important in reducing nasopharyngeal carriage. Mucosal immune responses to meningococcal conjugate and PS vaccines in young adults were investigated. Healthy university students were randomized to receive either a groups A+C meningococcal conjugate vaccine (MACconj, n = 100) or a group A+C meningococcal PS vaccine (MACPS, n = 95). One year after the primary immunization, both groups were randomized again to receive a MACconj or a MACPS booster vaccination. Saliva samples were collected before and 1 month after the primary and booster vaccinations. Anti-meningococcal A (MenA) and C (MenC) PS IgA and IgG antibody levels were measured by a standard enzyme-linked immunosorbent assay. After the primary vaccination, salivary MenA and MenC IgG and MenA IgA concentrations were significantly increased after immunization with both MACconj and MACPS vaccines, but the salivary Men C IgA level was increased only after MACPS vaccine (P < 0.01). IgA responses to both serogroups were greater for MACPS than MACconj vaccine (P < 0.05), whereas no significant differences were seen for IgG responses. MenA IgG titers were higher after the MACPS booster in MACconj-primed subjects than after the MACPS primary vaccination, suggesting the presence of IgG memory. Antibody responses to a dose of either MACPS or MACconj were not significantly reduced in those previously given MACPS compared to the primary responses to those vaccines. Meningococcal A+C conjugate and PS vaccines induce significant mucosal responses in young adults. MACconj priming may induce IgG memory at the mucosal level, which is likely to be a reflection of an anamnestic serum IgG response. No evidence of mucosal hyporesponsiveness was observed after MACPS priming in this study.

Adolescent↗