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Immunological characteristics of leukemia and lymphoma in allogeneic cell immunity: growth of syngeneic tumors in rats immunized with allogeneic cells.

The growth of transplanted tumors was strongly inhibited in syngeneic Wistar King Aptekman (WKA) rats immunized with allogeneic tumor cells from Donryu rats. This phenomenon of non-specific immunity against tumors is referred to as "allogeneic cell immunity". However, an exception to the "allogeneic cell immunity" was observed in leukemias and lymphomas. Four transplanted leukemia or lymphoma lines were not inhibited in syngeneic rats immunized with allogenic tumor cells. Furthermore, immunization with allogeneic leukemic cells had only a relatively weak inhibitory effect upon a syngeneic fibrosarcoma and no inhibitory effect upon leukemias. In WKA rats immunized with allogeneic lymphoid cells from Donryu rats, the growth of fibrosarcoma, but not of lymphoma, was inhibited. Using transplantation experiments, both fibrosarcoma and lymphoma were defined as antigenic tumors in WKA rats. Transplantation of mixtures of syngeneic tumor cells and allogeneic tumor cells in WKA rats confirmed the above findings. These results revealed that leukemia and lymphoma differ from non-leukemic tumors in regard to "allogeneic cell immunity".

Animals↗

Plasmodium falciparum: passive immunization of Aotus lemurinus griseimembra with immune serum.

Owl monkeys (Aotus lemurinus griseimembra) were immunized against Plasmodium falciparum by infection and drug cure. After challenge, 3 of 4 monkeys developed extended prepatent periods and low grade parasitemias followed by self cure. The fourth monkey did not develop a patent infection. Immune monkey serum passively transferred at the time of challenge conferred immunity to 20 naive monkeys. Immunity was characterized by extended prepatent periods in 19 monkeys, low levels of parasitemia (< or = 1%) followed by self cure in 12 animals, and lack of detectable infection in 3 recipient monkeys. Immune serum collected from monkeys undergoing repeated challenges afforded more protection than serum from singly infected monkeys. However, single doses of hyperimmune serum appeared to be as effective as multiple doses. Normal serum had no effect on the course of infection in 12 monkeys. These studies confirm that owl monkeys can be immunized by infection and cure and demonstrate that this immunity can, in large part, be transferred to nonimmune recipients with serum from immune donors.

Animals↗

Stimulation of local immunity and protection in mice by intramuscular immunization with triple- or double-layered rotavirus particles and QS-21.

Based on studies in animal models, parenteral immunization has become recognized as a potential vaccination strategy against rotavirus. Using an adult mouse model, the effects of the saponin adjuvant QS-21 on protection against murine rotavirus (strain EDIM) infection was determined following two intramuscular (i.m.) immunizations with purified EDIM particles including triple-layered (tl) infectious particles, tl particles inactivated with psoralen/UV, and double-layered (dl) inactivated particles. All three particles stimulated large serum rotavirus IgG responses and small amounts of serum rotavirus IgA, but undetectable stool rotavirus IgA. Inclusion of QS-21 during immunization increased the serum responses approximately 2- to 10-fold and also stimulated low levels of stool rotavirus IgA. Protection based on reduced shedding of rotavirus following EDIM challenge was significant (P < 0.001) with each immunized group and was enhanced (P < 0.001) by inclusion of QS-21 during immunization. Mice immunized with either live or inactivated tl particles and QS-21 were almost fully protected. Furthermore, animals inoculated with dl particles and the adjuvant shed significantly (P = .02) less virus following challenge than mice immunized with inactivated tl particles even though the latter induced measurable titers of neutralizing antibody to EDIM. These results demonstrate significant protection against rotavirus following i.m. immunization with both dl and tl EDIM particles which is consistently enhanced with QS-21.

Adjuvants, Immunologic↗

Cell-mediated immunity: correlation of mixed-leucocyte-macrophage migration inhibition with delayed-type hypersensitivity after immunization and donor-specific transfer of cell migration inhibition by dialyzable leucocyte extract.

Active and adoptive sensitization of rhesus monkeys (Macacca mulatta) as well as the development of a novel sensitive in vitro cell migration inhibition assay for cell-mediated immunity (CMI) in this species are described. First, the correlation of mixed leucocyte-macrophage migration tests (LMMI) with the whole blood lymphocyte transformation (LT) and the delayed hypersensitivity skin test (DH) in immunized animals are shown. Second, these tests are used to demonstrate adoptive transfer of specific/nonspecific cellular immunity (CMI) with dialyzable leucocyte extract (DLE) from immunized donor to unimmunized recipient monkeys. Seventeen animals were immunized with keyhole limpet haemocyanin (KLH) or hepatitis B surface antigen (HBsAg) in Freund's complete adjuvant (FCA) or with FCA alone. Acquisition of antigen-specific cell-mediated immunity was detected by all three tests within 5 weeks of immunization. Positive LMMI responses were associated with positive DH and LT. However, there was no correlation between the magnitude or time of development of the three responses. Therefore, the LMMI test, like the LT test, is an in vitro parameter of DH, but reflects the activity of different subpopulations of lymphocytes and is regulated by different mechanisms. In addition, 12 naive animals received DLE. Within 3 weeks, transfer of sensitivity was detected towards antigens to which the recipients had previously not been reactive but the donors had been. An enhancement of transformation response to phytohaemagglutinin was also seen. Thus, rhesus DLE contains both donor-specific transfer factor-like and nonspecific adjuvant-like activities. In DLE recipients, unlike immunized animals, LMMI responses were dissociated from DH or LT responses in that positive LMMI was mostly seen with negative DH or LT to antigens. Therefore, LMMI emerged as the most sensitive assay for detecting adoptive transfer of CMI by DLE in vivo, supporting the view that different mechanisms regulate LMMI, LT, and DH.

Animals↗

Correlation between in vivo humoral and in vitro cellular immune responses following immunization with hepatitis B surface antigen (HBsAg) vaccines.

To study the regulation of the human immune response to hepatitis B surface antigen (HBsAg) we have carefully monitored the in vivo humoral and in vitro cellular immune responses to HBsAg in 50 subjects receiving four doses of hepatitis B vaccine according to a 0, 1, 2, 12 month vaccination scheme. Twenty-three subjects were given a plasma-derived vaccine (Hevac B) and 27 received a recombinant HBsAg vaccine (yeast-derived; Engerix-B). The humoral and cellular immune responses were measured before vaccination (day 0); 6 days after the second dose (day 36); 6 days (day 66), 2 months (day 120) and 10 months (day 365) after the third dose and 1 month after the fourth dose (day 395). Based on the kinetics of the humoral immune responses, the vaccinees could be classified into fast, intermediate and slow/non-responders. Based on the magnitude of the immune response (anti-HBs titre) on day 395, the vaccinees could be divided into high (> or = 2000 U l-1) and low (< or = 2000 U l-1) responders. A close correlation between the kinetics and the magnitude of the humoral immune response was observed. The in vivo anti-HBs response was measured using commercially available immunoradiometric assays. The in vitro cellular immune response was measured using an HBsAg-specific lymphoproliferation assay. Because of interassay variability the results were considered as dichotomous variables (proliferation versus non-proliferation) for further data analysis. A statistically significant correlation was observed between the kinetics and magnitude of the humoral immune response on the one hand and the in vitro anti-HBs response on the other hand.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Humoral and cellular immune responses in the murine respiratory tract following oral immunization with cholera toxin or Escherichia coli heat-labile enterotoxin.

Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are the strongest mucosal immunogens identified to date and are also good adjuvants when given orally together in combination with unrelated antigens. We used these potent immunogens to monitor local and systemic immune responses following oral immunization of BALB/c mice, and compared their action on the following: (a) immunoglobulin production rates (IgG, IgM and IgA) in mucosal inductive (Peyer's patches-PPs), effector (intestinal lamina propria-LP, respiratory tract) and systemic (spleen) sites; (b) analysis of systemic antigen-specific antibodies (IgG subclasses, IgA and IgE); (c) time monitoring of fecal anti-CT and anti-LT antibodies, and (d) in vivo relevance of interleukin-6 (IL-6) to mucosal responses. Both mucosal immunogens elicited specific antibody responses (IgA, IgG) not only in the gastrointestinal tract (PP's and intestinal LP), but also in the respiratory tract and spleens of orally immunized mice. These mucosal responses were accompained by elevated secretion of IL-6 in all investigated tissues, indicating involvement of this cytokine in B-cell maturation processes. Furthermore, oral immunization with CT and LT induced elevated serum titers of IgG1 followed by IgG2a, IgG2b, IgG3 and IgA, while high antigen-specific IgA and IgG1 responses were found in fecal extracts. These findings illustrate the action of orally administered CT and LT, respectively, on several humoral and cellular immune responses not only at the gastrointestinal tract, the application site, but also in distant mucosal effector sites such as the respiratory tract. These data suggest the potential use of these mucosal adjuvants in oral immunization strategies to improve the local immune response in remote mucosal tissues, in accordance with the concept of a common mucosa-associated immune system.

Administration, Oral↗

HLA class I expression and tumor immune infiltration together shape colon cancer immune contexture.

BACKGROUND: The relative contribution of HLA class I molecules-including classical HLA class Ia (HLA-A, -B, -C) and non-classical HLA class Ib (HLA-E, -F, -G)-to shaping the tumor immune microenvironment in colon cancer remains insufficiently defined. We investigated how their expression patterns relate to immune infiltration and clinical outcome. METHODS: In a retrospective cohort of 280 colon cancers, we assessed HLA class Ia and class Ib expression and quantified CD45-positive immune cell infiltration by immunohistochemistry. These features were correlated with clinicopathological variables, microsatellite instability (MSI) status, and previously established genomic immune signatures. RESULTS: High HLA class Ia expression and increased CD45-positive cell infiltration were each associated with improved overall, disease-specific, and progression-free survival. CD45-positive density correlated strongly with Immunologic Constant of Rejection scores. HLA class Ia loss was more frequent in advanced stages and in MSI-H tumors. Among HLA class Ib molecules, only HLA-E expression was associated with favorable disease-specific and progression-free survival. Integrative analysis identified three immune phenotypes with distinct prognostic profiles; tumors characterized by high HLA class Ia expression, low HLA class Ib expression, and high CD45-positive infiltration had the best outcomes. CONCLUSION: Colon cancer immunogenicity is shaped by coordinated patterns of HLA class I expression and immune infiltration. Integrating HLA class Ia/Ib expression with immune cell density provides a refined stratification of tumor immune phenotypes and may support personalized immunotherapeutic decision-making.

Antigen presentation↗

Intestinal mucosal immune response in chickens following intraocular immunization with liposome-associated Salmonella enterica serovar enteritidis antigen.

Induction of intestinal mucosal immune responses against Salmonella enterica serovar enteritidis was studied by immunizing chickens with liposome-associated antigen. An ultrasonicated whole cell extract of the bacteria was used for immunizing antigen. Intraocular immunization induced serum IgA, IgG and IgM responses. Also, significant IgA and IgG antibodies were detected in the intestinal tract. Immunization with antigen alone induced only IgG response in the intestine. Salmonella enteritidis-specific antibody-secreting lymphocytes were detected in the spleen and lamina propria of the intestinal tract of immunized chickens. Immunoglobulin (Ig) fractions extracted from intestines of immunized chickens inhibited the adherence of S. enteritidis to cultured HeLa cells. These results indicate that intraocular immunization with liposome-associated S. enteritidis elicits specific antibody-producing lymphocytes in the intestinal tract, and that Ig secreted in the intestine inhibits adherence of the bacteria to intestinal epithelial cells, suppressing the spread of bacterial infection in the host.

Animals↗

Insect immunity: evolutionary roots of the mammalian innate immune system.

The innate immune system of vertebrates was considered as a survival of ancient antimicrobial systems that have become obsolescent by the emergence of adaptive immunity. Despite the fact that innate immunity lacks the elegance of genetic recombination mechanism to produce trillions of specific clones of immune cells and shows no memory, that view is out of date. Today, the innate immune system is rather regarded to be essential to the function of adaptive immunity by dictating the conduct of the acquired immune response [1] with the help of cytokines, complement, lectin receptors, antigen-reactive T-lymphocytes and B7.1, B7.2 proteins on B cells [2]. This review focuses on recent studies of insect immunology and summarises the currently known similarities between the innate immune system in insects and in vertebrates.

Animals↗

Intranasal immunization with formalin-inactivated virus vaccine induces a broad spectrum of heterosubtypic immunity against influenza A virus infection in mice.

It has been known that influenza A virus infection induces a cross-protective immunity against infection by viruses with different subtypes of viral envelope proteins, hemagglutinin (HA) and neuraminidase (NA). This heterosubtypic immunity is generally mediated by cytotoxic T lymphocytes (CTL) reactive to specific epitopes in the viral internal proteins, such as nucleoprotein and matrix protein. By contrast, immunization with inactivated virus antigens has been thought to be unable to generate heterosubtypic immunity, since inactivated antigens do not usually induce CTL responses. However, we show that intranasal immunization with formalin-inactivated intact virus, but not ether-split vaccines, induced a broad spectrum of heterosubtypic protective immunity in mice. The protection may be mediated by the mucosal immune response, most likely secretory IgA antibodies to the viral proteins. This approach may overcome limitations in the efficacy of inactivated influenza vaccines and confer potent immunity to humans against viruses with new pandemic potential.

Administration, Intranasal↗

DNA immunization targeting the skin: molecular control of adaptive immunity.

DNA-based immunization represents a novel approach for vaccine development. Recombinant DNA techniques are used to clone DNA sequences encoding antigens of choice into eukaryotic expression plasmids, which are readily and economically amplified in bacteria and recovered with a high degree of purity. For immunization, plasmid DNA is either coated onto microscopic gold particles and bombarded into skin using a gene gun or injected into skin or muscle. Expression of administered genes results in the induction of humoral and cellular immune responses against the encoded antigen. DNA immunization is capable of inducing protective immunity in a number of animal models of infectious disease and cancer. Recent studies suggest that antigen-specific cytotoxic T lymphocyte induction occurs through the presentation of appropriate peptides in the context of major histocompatibility complex molecules on bone marrow-derived professional antigen presenting cells. Following DNA inoculation into the skin, Langerhans cells and/or dermal dendritic cells are believed to acquire the newly synthesized antigen, either through direct transfection or via antigen uptake from transfected keratinocytes, and migrate to regional lymph nodes where they stimulate primary T cell responses. The nature of the immune response depends on the route, method, and timing of DNA delivery and can also be influenced by co-delivery of plasmids encoding immunomodulating cytokines like IFN-alpha, IL-2, or IL-12 and costimulatory molecules like B7-1. While many aspects of the biology of cutaneous DNA immunization remain unknown, the skin appears to offer unique potential as a target for DNA-based immunization.

Animals↗

Immune response to chemically modified flagellin. II. Evidence for a fundamental relationship between humoral and cell-mediated immunity.

Flagellin (mol.wt. 40,000) from S. adelaide organisms and a series of acetoacetyl derivatives of flagellin were tested for their ability to induce humoral and cell-mediated immunity in adult rats. It was found that unmodified flagellin was an excellent inducer of antibody formation but a poor inducer of delayed-type hypersensitivity. In contrast, increasing acetoacetylation steadily destroyed the ability of flagellin to initiate antibody formation but enhanced the capacity of the molecule to induce flagellin-specific cell-mediated immunity and antibody tolerance. In fact, it appeared that in adult rats antibody formation and cell-mediated immunity may well be opposing immunological processes. Furthermore, the affinity of the acetoacetyl flagellins for anti-flagellin antibodies appeared to determine the type of immune response which predominated. High affinity antigen produced antibody formation whereas low affinity antigen induced cell-mediated immunity and antibody tolerance. The importance of affinity was further evidenced by the fact that a CNBr digest of flagellin induced humoral and cellular immune responses identical to an acetoacetylated flagellin of comparable antigenic activity. From these studies it was proposed that both humoral and cell-mediated immunity can be directed against the same antigenic determinants but that the specificity requirements for delayed hypersensitivity (and antibody tolerance) are less than those required for antibody formation. Some remarkable immunological features of the flagellin system were revealed. Flagellin induced comparable delayed-type hypersensitivity when injected in either saline or FCA. Furthermore, FCA only slightly enhanced the delayed responses induced by the acetoacetyl flagellins and in fact these preparations produced antibody tolerance whether injected in saline or adjuvant. Finally, in contrast to the adult tolerance induced by the acetoacetylated flagellins, which existed only at the antibody level, tolerance in neonatal rats existed at the level of both humoral and cell-mediated immunity. This finding is the first indication of a fundamental difference between neonatal and adult tolerance. The significance of these findings is discussed in the light of current immunological concepts and a hypothesis proposed to explain these phenomena.

Acetoacetates↗

Antigen recognition and the immune response. Humoral and cellular immune responses to small mono- and bifunctional antigen molecules.

L-Tyrosine azobenzene-p-arsonate (RAT) induced cellular immunity without antibody production in guinea pigs. Bifunctional antigens were prepared consisting of one RAT carrier moiety linked either directly to a dinitrophenyl (DNP) haptenic determinant or through one or more 6-amino-caproyl (SAC) spacers. Each SAC unit has an extended span of 8 A. Guinea pigs immunized with these conjugates developed cellular immunity directed against the RAT determinant and antibody specific for the DNP determinant. The anti-DNP response was the same with one or three SAC spacers, but was significantly weaker when the two determinants were joined without a spacer. Animals immunized with either DNP-SAC-TYR or DNP-TYR developed neither cellular nor humoral immunity. Prior immunization with RAT potentiated the secondary anti-hapten response to DNP-SAC-RAT. Modification of RAT at either the arsonate or tyrosine positions showed that other charged groups (sulfonate and trimethylammonium) could substitute for arsonate without loss of immunogenicity. Removal of either the amino or carboxyl group from the side chain of tyrosine did not abolish immunogenicity, but immunogenicity was lost upon removal of both. Immunization with symmetrical bifunctional RAT-(SAC)(n)-RAT and cyclo-(L-RAT-D-RAT) antigens led to cellular immunity but no anti-arsonate antibody, suggesting a barrier to "self-help." These compounds were also ineffective in inducing a secondary anti-arsonate response in animals primed with arsonate-BSA conjugates and RAT.

Animals↗

The effect of route of immunization on mucosal immunity and protection.

In macaques, the route of immunization has a profound effect on the immune response. Augmenting rectal or vaginal immunization with oral or nasal immunization enhanced the secretory IgA, serum IgG, and T cell responses. However, targeted iliac lymph node (TILN) immunization with recombinant simian immunodeficiency virus (SIV) gp120 and p27 elicited the most consistent mucosal antibody responses in the rectum, vagina, urine, seminal fluid, and blood. Both mucosal and TILN immunization induced specific CD4+ T cell proliferative responses in the iliac lymph nodes, which drain these mucosal surfaces, and in the splenic and circulating T cells. Rectal mucosal challenge with cell-free SIV induced total protection in 4 of 7 macaques that were immunized by the TILN route, and, compared with unimmunized macaques or those immunized by the mucosal route (P<.001), it induced a >90% decrease in virus load in 3 of them. Protection from mucosal rectal infection with SIV was significantly associated with an increase in the CD8 suppressor factor (which was generated by the iliac lymph node), RANTES, and MIP-1beta (P<.01).

Animals↗

Effect of maternal immunization with oral poliovirus vaccine on neonatal immunity.

During the summer of 1988, an outbreak of poliomyelitis caused by poliovirus 1 occurred in Israel, during which a national mass immunization campaign with oral poliovirus was undertaken. This prospective study was undertaken to assess the effect of maternal oral poliovirus immunization during the third trimester of pregnancy on neonatal immunity against poliovirus. Cord blood specimens of 88 neonates, born 2 to 7 weeks after maternal immunization, were examined for antipoliovirus antibodies and compared with 100 samples obtained from neonates 7 months before the outbreak. Blood samples were also obtained from the 62 mothers of neonates who had been immunized 2 to 5 weeks before delivery. Sera were tested for neutralizing antibodies to the 3 poliovirus types using a microneutralization technique. The geometric mean titer to poliovirus type 1 was significantly higher in neonates whose mothers were immunized during pregnancy (87.1) than in the offspring of the nonvaccinated group (53.0), P < 0.05. Two to 3 weeks after immunization, geometric mean titers against all 3 poliovirus types were higher in maternal blood than in cord blood whereas 4 to 5 weeks after vaccination a significant difference was found for type 3 only. Although oral poliovirus immunization during pregnancy resulted in higher neonatal antibody titers to poliovirus type 1, the proportion of newborns with titers of < 1:8 to the 3 poliovirus types did not change significantly.

Antibodies, Viral↗

Immune response to ultraviolet-induced tumors. II. Effector cells in tumor immunity.

Skin tumors induced in mice by chronic ultraviolet irradiation are highly antigenic and can induce a state of transplantation immunity in syngeneic hosts. In the present study, we compared the in vitro cytolytic activity of splenic lymphocytes from mice immunized with either a regressor or a progressor UV-tumor. The results of this comparison supported previous work implicating a role for tumor-specific cytolytic T lymphocytes in the rejection of regressor UV-tumors. The results also revealed that immunization with the progressor UV-tumor 2237 failed to elicit detectable levels of progressor tumor-specific CTL in animals capable of rejecting the immunizing tumor. Interestingly, following in vitro resensitization of both regressor and progressor immune spleen cells, we found a previously undetected lymphocyte population with anti-UV-tumor activity. Besides lysing UV-tumors in vitro, these lymphocytes also lysed a wide variety of additional tumor targets. This effector activity along with the analysis of cell surface markers indicated that these lymphocytes belong to that category of effector cells mediating natural-cell-mediated cytotoxicity (NCMC). As we had not detected cells with this activity in splenic lymphocyte preparations prior to in vitro resensitization, we examined lymphocytes from the local tumor environment during the course of progressor 2237 tumor rejection for either NCMC activity or tumor-specific CTL activity. This in situ analysis revealed lymphocytes exhibiting significant levels of cytolytic activity against several UV-tumors, thus implicating NK cells as effector cells in the rejection of progressor UV-tumors by immune animals. The mechanisms whereby NK cells with NCMC activity could be induced in immune animals are discussed in the context of class-II-restricted immune responses by helper/inducer T lymphocytes.

Animals↗

Oral vaccination with modified vaccinia virus Ankara attached covalently to TMPEG-modified cationic liposomes overcomes pre-existing poxvirus immunity from recombinant vaccinia immunization.

Development of a safe and effective vaccine for induction of mucosal immunity to the human immunodeficiency virus (HIV) envelope glycoprotein (Env, gp160) represents the best hope for containing the spread of an HIV epidemic worldwide. The highly attenuated modified vaccinia virus Ankara (MVA) is a laboratory virus well suited as a safe vaccine vector. However, the presence of pre-existing immunity to Vaccinia virus in the adult population represents a hindrance that limits the application of the MVA vector for inducing immunity to HIV antigens. Here, cationic liposomes were covalently attached to the surface of recombinant MVA expressing the HIV-1 strain IIIB Env glycoprotein and beta-galactosidase (MVA(IIIB/beta-gal)) using tresylmonomethoxypolyethylene glycol (TMPEG) grafted into a lipid membrane without compromising viral infectivity in vitro and in vivo. The orally administered MVA(IIIB/beta-gal)-TMPEG/liposome complexes were capable of delivering the transgenes to mucosal tissues in mice with pre-existing poxvirus immunity based on beta-galactosidase gene expression in intestinal tissues measured 18 h after infection. Importantly, the MVA(IIIB/beta-gal)-TMPEG/liposome complexes enhanced Env-specific cellular and humoral immune responses in the mucosal and systemic tissues after repeated oral immunization of BALB/c mice. This approach may prove useful for induction of protective immunity against infectious diseases and cancer in populations with pre-existing immunity to vaccinia from smallpox vaccination.

Adjuvants, Immunologic↗

Differential polarization of immune responses by genetic cotransfer of chemokines changes the protective immunity of DNA vaccine against pseudorabies virus.

Chemokines play a key role in eliciting adaptive immune responses by selectively attracting the innate cellular components to the site of antigen presentation. To evaluate the effect of the genetic adjuvant of chemokines on the adaptive immune responses induced by a plasmid DNA vaccine expressing glycorotein B (gB) of the pseudorabies virus (PrV), a PrV DNA vaccine was co-inoculated with plasmid DNA expressing certain chemokines including CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CCL5 (RANTES), CXCL8 (MIP-2), and CXCL10 (IP-10). A co-injection of the CCL3 plasmid DNA induced immunity that was biased to the T helper type 2 (Th2) pattern, as judged by the ratio of immunoglobulin G isotypes and the production of interleukin-4 cytokine generated from stimulated immune T cells. However, CCL5 and CXCL10 induced immune responses of the Th1-type, which rendered the recipients more resistant to a virulent virus infection. CXCL8 also showed enhanced humoral and cell-mediated immunity (mixed-type pattern) providing effective protection against a viral challenge. However, there was no change in the immune responses induced by the PrV DNA vaccine in CCL4 recipients. These results suggest that co-injection of a chemokine, in the form of an adjuvant preparation, causes a rebalancing of the immunity, which subsequently affects the protective efficacy against a virulent virus infection.

Animals↗