Cellular Immune Responses to Neisseria meningitidis in Children

ABSTRACT There is an urgent need for effective vaccines against serogroup BNeisseria meningitidis. Current experimental vaccines based on the outer membrane proteins (OMPs) of this organism provide a measure of protection in older children but have been ineffective in infants. We postulated that the inability of OMP vaccines to protect infants might be due to age-dependent defects in cellular immunity. We measured proliferation and in vitro production of gamma interferon (IFN-γ), tumor necrosis factor alpha, and interleukin-10 (IL-10) in response to meningococcal antigens by peripheral blood mononuclear cells (PBMCs) from children convalescing from meningococcal disease and from controls. After meningococcal infection, the balance of cytokine production by PBMCs from the youngest children was skewed towards a TH1 response (low IL-10/IFN-γ ratio), while older children produced more TH2 cytokine (higher IL-10/IFN-γ ratio). There was a trend to higher proliferative responses by PBMCs from older children. These responses were not influenced by the presence or subtype of class 1 (PorA) OMP or by the presence of class 2/3 (PorB) or class 4 OMP. Even young infants might be expected to develop adequate cellular immune responses to serogroup B N. meningitidis vaccines if a vaccine preparation can be formulated to mimic the immune stimulus of invasive disease, which may include stimulation of TH2 cytokine production.

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Simultaneous Administration of Recombinant Measles Viruses Expressing Respiratory Syncytial Virus Fusion (F) and Nucleo (N) Proteins Induced Humoral and Cellular Immune Responses in Cotton Rats

Vaccines ◽

10.3390/vaccines7010027 ◽

2019 ◽

Vol 7 (1) ◽

pp. 27 ◽

Cited By ~ 2

Author(s):

Yoshiaki Yamaji ◽

Akihito Sawada ◽

Yosuke Yasui ◽

Takashi Ito ◽

Tetsuo Nakayama

Keyword(s):

Respiratory Syncytial Virus ◽

Immune Responses ◽

Neutralizing Antibodies ◽

Simultaneous Administration ◽

Cellular Immune Responses ◽

Immunization Group ◽

Cotton Rats ◽

Ifn Γ ◽

Syncytial Virus ◽

Cellular Immune

We previously reported that recombinant measles virus expressing the respiratory syncytial virus (RSV) fusion protein (F), MVAIK/RSV/F, induced neutralizing antibodies against RSV, and those expressing RSV-NP (MVAIK/RSV/NP) and M2-1 (MVAIK/RSV/M2-1) induced RSV-specific CD8+/IFN-γ+ cells, but not neutralizing antibodies. In the present study, MVAIK/RSV/F and MVAIK/RSV/NP were simultaneously administered to cotton rats and immune responses and protective effects were compared with MVAIK/RSV/F alone. Sufficient neutralizing antibodies against RSV and RSV-specific CD8+/IFN-γ+ cells were observed after re-immunization with simultaneous administration. After the RSV challenge, CD8+/IFN-γ+ increased in spleen cells obtained from the simultaneous immunization group in response to F and NP peptides. Higher numbers of CD8+/IFN-γ+ and CD4+/IFN-γ+ cells were detected in lung tissues from the simultaneous immunization group after the RSV challenge. No detectable RSV was recovered from lung homogenates in the immunized groups. Mild inflammatory reactions with the thickening of broncho-epithelial cells and the infiltration of inflammatory cells were observed in lung tissues obtained from cotton rats immunized with MVAIK/RSV/F alone after the RSV challenge. No inflammatory responses were observed after the RSV challenge in the simultaneous immunization groups. The present results indicate that combined administration with MVAIK/RSV/F and MVAIK/RSV/NP induces humoral and cellular immune responses and shows effective protection against RSV, suggesting the importance of cellular immunity.

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Humoral and Cellular Immune Responses to Trypanosoma cruzi-Derived Paraflagellar Rod Proteins in Patients with Chagas' Disease

Infection and Immunity ◽

10.1128/iai.71.6.3165-3171.2003 ◽

2003 ◽

Vol 71 (6) ◽

pp. 3165-3171 ◽

Cited By ~ 34

Author(s):

Vladimir Michailowsky ◽

Keith Luhrs ◽

Manoel Otávio C. Rocha ◽

David Fouts ◽

Ricardo T. Gazzinelli ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Immune Responses ◽

Chagas Disease ◽

Mononuclear Cells ◽

Clinical Symptoms ◽

Cellular Responses ◽

Peripheral Blood Mononuclear ◽

Cellular Immune Responses ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4+ CD25+ and CD4+ CD69+ lymphocytes, as well as that of small CD8+ CD25+ lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-γ) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-γ upon stimulation with PFR. PFR enhanced the percentages of IFN-γ-producing cells in both CD3+ and CD3− populations. Within the T-cell population, large CD4+ T lymphocytes were the main source of IFN-γ.

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Molecular and Immunological Significance of Chimpanzee Major Histocompatibility Complex Haplotypes for Hepatitis C Virus Immune Response and Vaccination Studies

Journal of Virology ◽

10.1128/jvi.76.12.6093-6103.2002 ◽

2002 ◽

Vol 76 (12) ◽

pp. 6093-6103 ◽

Cited By ~ 22

Author(s):

Eishiro Mizukoshi ◽

Michelina Nascimbeni ◽

Joshua B. Blaustein ◽

Kathleen Mihalik ◽

Charles M. Rice ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Major Histocompatibility Complex ◽

Hepatitis C ◽

Immune Responses ◽

Cellular Immune Responses ◽

Functional Homology ◽

Histocompatibility Complex ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT The chimpanzee is a critical animal model for studying cellular immune responses to infectious pathogens such as hepatitis B and C viruses, human immunodeficiency virus, and malaria. Several candidate vaccines and immunotherapies for these infections aim at the induction or enhancement of cellular immune responses against viral epitopes presented by common human major histocompatibility complex (MHC) alleles. To identify and characterize chimpanzee MHC class I molecules that are functionally related to human alleles, we sequenced 18 different Pan troglodytes (Patr) alleles of 14 chimpanzees, 2 of them previously unknown and 3 with only partially reported sequences. Comparative analysis of Patr binding pockets and binding assays with biotinylated peptides demonstrated a molecular homology between the binding grooves of individual Patr alleles and the common human alleles HLA-A1, -A2, -A3, and -B7. Using cytotoxic T cells isolated from the blood of hepatitis C virus (HCV)-infected chimpanzees, we then mapped the Patr restriction of these HCV peptides and demonstrated functional homology between the Patr-HLA orthologues in cytotoxicity and gamma interferon (IFN-γ) release assays. Based on these results, 21 HCV epitopes were selected to characterize the chimpanzees' cellular immune response to HCV. In each case, IFN-γ-producing T cells were detectable in the blood after but not prior to HCV infection and were specifically targeted against those HCV peptides predicted by Patr-HLA homology. This study demonstrates a close functional homology between individual Patr and HLA alleles and shows that HCV infection generates HCV peptides that are recognized by both chimpanzees and humans with Patr and HLA orthologues. These results are relevant for the design and evaluation of vaccines in chimpanzees that can now be selected according to the most frequent human MHC haplotypes.

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Magnitude and Phenotype of Cellular Immune Responses Elicited by Recombinant Adenovirus Vectors and Heterologous Prime-Boost Regimens in Rhesus Monkeys

Journal of Virology ◽

10.1128/jvi.02616-07 ◽

2008 ◽

Vol 82 (10) ◽

pp. 4844-4852 ◽

Cited By ~ 93

Author(s):

Jinyan Liu ◽

Bonnie A. Ewald ◽

Diana M. Lynch ◽

Matthew Denholtz ◽

Peter Abbink ◽

...

Keyword(s):

Immune Responses ◽

T Lymphocyte ◽

Rhesus Monkeys ◽

Recombinant Adenovirus ◽

Interleukin 2 ◽

Cellular Immune Responses ◽

Tnf Α ◽

Ifn Γ ◽

Cellular Immune ◽

Lymphocyte Responses

ABSTRACT Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-γ+) and IFN-γ+/tumor necrosis factor alpha+ (TNF-α+) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2+ (IL-2+) and polyfunctional IFN-γ+/TNF-α+/IL-2+ T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8+ and CD4+ T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.

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Th-1-Type Cytotoxic CD8+ T-Lymphocyte Responses to Simian Immunodeficiency Virus (SIV) Are a Consistent Feature of Natural SIV Infection in Sooty Mangabeys

Journal of Virology ◽

10.1128/jvi.80.6.2771-2783.2006 ◽

2006 ◽

Vol 80 (6) ◽

pp. 2771-2783 ◽

Cited By ~ 50

Author(s):

Zichun Wang ◽

Benjamin Metcalf ◽

Ruy M. Ribeiro ◽

Harold McClure ◽

Amitinder Kaur

Keyword(s):

T Lymphocytes ◽

Immune Responses ◽

Rhesus Macaques ◽

Elispot Response ◽

Cellular Immune Responses ◽

Immunodeficiency Virus ◽

Sooty Mangabeys ◽

Siv Infection ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT Sooty mangabeys are a natural host of simian immunodeficiency virus (SIV) that remain asymptomatic and do not exhibit increased immune activation or increased T-lymphocyte turnover despite sustained high levels of SIV viremia. In this study we asked whether an altered immune response to SIV contributes to the lack of immunopathology in sooty mangabeys as opposed to species with pathogenic lentivirus infection. SIV-specific cellular immune responses were investigated in a cohort of 25 sooty mangabeys with natural SIV infection. Gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses targeting a median of four SIV proteins were detected in all 25 mangabeys and were comparable in magnitude to those of 13 rhesus macaques infected with SIVmac251 for more than 6 months. As with rhesus macaques, Th2 ELISPOT responses to SIV were absent or >10-fold lower than the IFN-γ ELISPOT response to the same SIV protein. The SIV-specific ELISPOT response was predominantly mediated by CD8+ T lymphocytes; the frequency of circulating SIV-specific CD8+ T lymphocytes ranged between 0.11% and 3.26% in 13 mangabeys. Functionally, the SIV-specific CD8+ T lymphocytes were cytotoxic; secreted IFN-γ, tumor necrosis factor alpha, and macrophage inflammatory protein 1β; and had an activated effector phenotype. Although there was a trend toward higher frequencies of SIV-specific CD8+ T lymphocytes in mangabeys with lower viral loads, a significant inverse correlation between SIV viremia and SIV-specific cellular immunity was not detected. The consistent detection of Th1-type SIV-specific cellular immune responses in naturally infected sooty mangabeys suggests that immune attenuation is neither a feature of nor a requirement for maintenance of nonpathogenic SIV infection in its natural host.

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BacMam virus-based surface display for HCV E2 glycoprotein induces strong cross-neutralizing antibodies and cellular immune responses in vaccinated mice

Infectious Agents and Cancer ◽

10.1186/s13027-021-00407-x ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ebrahim Kord ◽

Farzin Roohvand ◽

Jean Dubuisson ◽

Thibaut Vausselin ◽

Hosein Nasr Azadani ◽

...

Keyword(s):

Immune Responses ◽

Mammalian Cells ◽

Neutralizing Antibodies ◽

Surface Display ◽

Immunogold Electron Microscopy ◽

Cellular Immune Responses ◽

Boost Immunization ◽

Ifn Γ ◽

Cellular Immune ◽

And Control

Abstract Background Despite recent advancements, limitations in the treatment and control of hepatitis C virus (HCV) infection reprioritized the studies for invention of an efficient HCV vaccine to elicit strong neutralizing antibodies (NAbs) and cellular responses. Methods Herein, we report molecular construction of a BacMam virus-based surface display for a subtype-1a HCV gpE2 (Bac-CMV-E2-gp64; Bac) that both expressed and displayed gpE2 in mammalian cells and bacouloviral envelope, respectively. Results Assessments by western blotting, Immunofluorescence and Immunogold-electron microscopy indicated the proper expression and incorporation in insect cell and baculovirus envelope, respectively. Mice immunized in three different prime-boost immunization groups of: Bac/Bac, Bac/Pro (bacoulovirus-derived gpE2) and Bac/DNA (plasmid DNA (pCDNA)-encoding gpE2) developed high levels of IgG and IFN-γ (highest for Bac/Bac group) indicating the induction of both humeral and cellular immune responses. Calculation of the IgG2a/IgG1 and IFN-γ/IL-4 ratios indicated a Th1 polarization of immune responses in the Bac/Bac and Bac/DNA groups but a balanced Th1-Th2 phenotype in the Bac/Pro group. Sera of the mice in the Bac/Bac group provided the highest percentage of cross-NAbs against a subtype-2a HCVcc (JFH1) compared to Bac/Pro and Bac/DNA groups (62% versus 41% and 6%). Conclusions Results indicated that BacMam virus-based surface display for gpE2 might act as both subunit and DNA vaccine and offers a promising strategy for development of HCV vaccine for concurrent induction of strong humoral and cellular immune responses.

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Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

Pathogens ◽

10.3390/pathogens9100855 ◽

2020 ◽

Vol 9 (10) ◽

pp. 855

Author(s):

Jéssica Adriana Jesus ◽

Thays Nicolli Fragoso da Silva ◽

Eduardo Seiji Yamamoto ◽

João Henrique G. Lago ◽

Márcia Dalastra Laurenti ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Immune Responses ◽

Cutaneous Leishmaniasis ◽

Ursolic Acid ◽

Pharmacological Activities ◽

Cellular Immune Responses ◽

Highly Active ◽

Broad Array ◽

Ifn Γ ◽

Cellular Immune

Ursolic acid (UA) is a triterpene with a broad array of pharmacological activities. In leishmaniasis, UA killed different species of parasites, and it was active in the experimental model of cutaneous and visceral leishmaniasis. Thus, the objective of this work was to study the therapeutic efficacy of the conventional drugs amphotericin B (AmB) or glucantime (Glu) combined with UA in experimental visceral and cutaneous leishmaniasis, respectively. L. (L.) infantum-infected hamsters were treated with AmB alone or combined with UA. L. (L.) amazonensis-infected BALB/c mice were treated with Glu alone or combined with UA. Animals were treated for 15 consecutive days by intraperitoneal or intralesional routes. Following one week after the last dose, the tissue parasitism and cellular immune responses were analyzed. Hamsters treated with 0.2 and 1.0 mg/kg of AmB plus 1.0 mg/kg of UA showed low hepatic and splenic parasitisms; however, AmB given as monotherapy did not reduce the number of viable parasites in the spleen of treated animals. In cutaneous leishmaniasis, Glu given as monotherapy was inactive at 2.0 mg/kg, showed mild activity at 10.0 mg/kg, and at 50.0 mg/kg was highly active at eliminating parasites in the skin. When animals were treated with Glu plus UA, higher leishmanicidal activity was observed in comparison to all groups treated with monotherapy schemes, and such activity was related to lesion improvement and upregulation of IFN-γ production. Altogether, data suggest that the association of drugs for the treatment of leishmaniasis can increase the efficiency of the treatment and decrease the toxicity associated to the conventional drugs.

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Development of a novel, guinea pig-specific IFN-γ ELISPOT assay and characterization of guinea pig cytomegalovirus GP83-specific cellular immune responses following immunization with a modified vaccinia virus Ankara (MVA)-vectored GP83 vaccine

Vaccine ◽

10.1016/j.vaccine.2014.05.011 ◽

2014 ◽

Vol 32 (31) ◽

pp. 3963-3970 ◽

Cited By ~ 15

Author(s):

Peter A. Gillis ◽

Nelmary Hernandez-Alvarado ◽

Josephine S. Gnanandarajah ◽

Felix Wussow ◽

Don J. Diamond ◽

...

Keyword(s):

Immune Responses ◽

Guinea Pig ◽

Vaccinia Virus ◽

Elispot Assay ◽

Cellular Immune Responses ◽

Modified Vaccinia Virus Ankara ◽

Guinea Pig Cytomegalovirus ◽

Ifn Γ ◽

Cellular Immune

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Newborn Mice Vaccination with BCG.HIVA222+ MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

Clinical and Developmental Immunology ◽

10.1155/2011/516219 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Narcís Saubi ◽

Eung-Jun Im ◽

Raquel Fernández-Lloris ◽

Olga Gil ◽

Pere-Joan Cardona ◽

...

Keyword(s):

Immune Responses ◽

The Body ◽

Spleen Cells ◽

Vaccination Regimen ◽

Newborn Mice ◽

Cellular Immune Responses ◽

Adult Mice ◽

Ifn Γ ◽

Cellular Immune ◽

Hiv 1

We have evaluated the influence of age and immunization routes for induction of HIV-1- andM. tuberculosis-specific immune responses after neonatal (7 days old) and adult (7 weeks old) BALB/c mice immunization with BCG.HIVA222prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine.

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