scholarly journals Cellular Immune Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent HPV Vaccine in Fijian Girls and Subsequent Responses to a Dose of Bivalent HPV Vaccine

2018 ◽  
Vol 5 (7) ◽  
Author(s):  
Zheng Quan Toh ◽  
Kathleen Wen Bei Cheow ◽  
Fiona M Russell ◽  
Edwin Hoe ◽  
Rita Reyburn ◽  
...  

Abstract Background This study examined the cellular immunity of 0, 1, 2, and 3 doses of Gardasil vaccine (4vHPV) in girls after 6 years and their responses to a subsequent dose of Cervarix vaccine (2vHPV). Methods A subset of girls (n = 59) who previously received 0, 1, 2, or 3 doses of 4vHPV 6 years earlier were randomly selected from a cohort study of Fijian girls (age 15–19 years). Blood was collected before and 28 days after a dose of 2vHPV. The HPV16- and HPV18-specific cellular immune response was determined by IFNγ-ELISPOT and by measurement of cytokines in peripheral blood mononuclear cell supernatants. Results Six years after 4vHPV vaccination, HPV18-specific responses were significantly lower in the 1- (1D) or 2-dose (2D) recipients compared with 3-dose recipients (2D: IFNγ-ELISPOT: P = .008; cytokines, IFNγ: P = .002; IL-2: P = .022; TNFα: P = .016; IL-10: P = .018; 1D: IL-2: P = .031; IL-10: P = .014). These differences were no longer significant post-2vHPV. No significant differences in HPV16 responses (except IL-2, P < .05) were observed between the 2- or 1-dose recipients and 3-dose recipients. Conclusions These data suggest that cellular immunity following reduced-dose schedules was detectable after 6 years, although the responses were variable between HPV types and dosage groups. The clinical significance of this is unknown. Further studies on the impact of reduced dose schedules are needed, particularly in high–disease burden settings.

2021 ◽  
Author(s):  
Nicholas Kim Huat Khoo ◽  
Joey Ming Er Lim ◽  
Upkar Singh Gill ◽  
Ruklanthi de Alwis ◽  
Nicole Tan ◽  
...  

Protection offered by COVID-19 vaccines wanes over time, requiring an evaluation of different boosting strategies to revert such a trend and enhance the quantity and quality of Spike-specific humoral and cellular immune responses. These immunological parameters in homologous or heterologous vaccination boosts have thus far been studied for mRNA and ChAdOx1 nCoV-19 vaccines, but knowledge on individuals who received a single dose of Ad26.COV2.S is lacking. We studied Spike-specific humoral and cellular immunity in Ad26.COV2.S vaccinated individuals (n=55) who were either primed with Ad26.COV2.S only (n=13), or boosted with a homologous (Ad26.COV2.S, n=28) or heterologous (BNT162b2, n=14) second dose. We compared our findings with the results found in individuals vaccinated with a single (n=16) or double (n=44) dose of BNT162b2. We observed that a strategy of heterologous vaccination enhanced the quantity and breadth of both, Spike-specific humoral and cellular immunity in Ad26.COV2.S vaccinated. In contrast, the impact of homologous boost was quantitatively minimal in Ad26.COV2.S vaccinated and Spike-specific antibodies and T cells were narrowly focused to the S1 region. Although a direct association between quantity and quality of immunological parameters and in vivo protection has not been demonstrated, the immunological features of Spike-specific humoral and cellular immune responses support the utilization of a heterologous strategy of vaccine boost in individuals who received Ad26.COV2.S vaccination.


2003 ◽  
Vol 71 (6) ◽  
pp. 3165-3171 ◽  
Author(s):  
Vladimir Michailowsky ◽  
Keith Luhrs ◽  
Manoel Otávio C. Rocha ◽  
David Fouts ◽  
Ricardo T. Gazzinelli ◽  
...  

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.


2015 ◽  
Vol 90 (1) ◽  
pp. 332-344 ◽  
Author(s):  
Michela Brazzoli ◽  
Diletta Magini ◽  
Alessandra Bonci ◽  
Scilla Buccato ◽  
Cinzia Giovani ◽  
...  

ABSTRACTSeasonal influenza is a vaccine-preventable disease that remains a major health problem worldwide, especially in immunocompromised populations. The impact of influenza disease is even greater when strains drift, and influenza pandemics can result when animal-derived influenza virus strains combine with seasonal strains. In this study, we used the SAM technology and characterized the immunogenicity and efficacy of a self-amplifying mRNA expressing influenza virus hemagglutinin (HA) antigen [SAM(HA)] formulated with a novel oil-in-water cationic nanoemulsion. We demonstrated that SAM(HA) was immunogenic in ferrets and facilitated containment of viral replication in the upper respiratory tract of influenza virus-infected animals. In mice, SAM(HA) induced potent functional neutralizing antibody and cellular immune responses, characterized by HA-specific CD4 T helper 1 and CD8 cytotoxic T cells. Furthermore, mice immunized with SAM(HA) derived from the influenza A virus A/California/7/2009 (H1N1) strain (Cal) were protected from a lethal challenge with the heterologous mouse-adapted A/PR/8/1934 (H1N1) virus strain (PR8). Sera derived from SAM(H1-Cal)-immunized animals were not cross-reactive with the PR8 virus, whereas cross-reactivity was observed for HA-specific CD4 and CD8 T cells. Finally, depletion of T cells demonstrated that T-cell responses were essential in mediating heterologous protection. If the SAM vaccine platform proves safe, well tolerated, and effective in humans, the fully synthetic SAM vaccine technology could provide a rapid response platform to control pandemic influenza.IMPORTANCEIn this study, we describe protective immune responses in mice and ferrets after vaccination with a novel HA-based influenza vaccine. This novel type of vaccine elicits both humoral and cellular immune responses. Although vaccine-specific antibodies are the key players in mediating protection from homologous influenza virus infections, vaccine-specific T cells contribute to the control of heterologous infections. The rapid production capacity and the synthetic origin of the vaccine antigen make the SAM platform particularly exploitable in case of influenza pandemic.


2012 ◽  
Vol 302 (2) ◽  
pp. F276-F283 ◽  
Author(s):  
Hao Wang ◽  
Qiunong Guan ◽  
Zhu Lan ◽  
Shuyuan Li ◽  
Wei Ge ◽  
...  

Both humoral and cellular immune responses are involved in renal allograft rejection. Interleukin (IL)-6 is a regulatory cytokine for both B and Foxp3 (forkhead box P3)-expressing regulatory T (Treg) cells. This study was designed to investigate the impact of donor IL-6 production on renal allograft survival. Donor kidneys from IL-6 knockout (KO) vs. wild-type (WT) C57BL/6 mice (H-2b) were orthotopically transplanted to nephrotomized BALB/c mice (H-2d). Alloantibodies and Treg cells were examined by fluorescence-activated cell sorting analysis. Graft survival was determined by the time to graft failure. Here, we showed that a deficiency in IL-6 expression in donor kidneys significantly prolonged renal allograft survival compared with WT controls. IL-6 protein was upregulated in renal tubules and endothelium of renal allografts following rejection, which correlated with an increase in serum IL-6 compared with that in those receiving KO grafts or naive controls. The absence of graft-producing IL-6 or lower levels of serum IL-6 in the recipients receiving IL-6 KO allografts was associated with decreased circulating anti-graft alloantibodies and increased the percentage of intragraft CD4+CD25+Foxp3+ Treg cells compared with those with WT allografts. In conclusion, the lack of graft-producing IL-6 significantly prolongs renal allograft survival, which is associated with reduced alloantibody production and/or increased intragraft Treg cell population, implying that targeting donor IL-6 may effectively prevent both humoral and cellular rejection of kidney transplants.


Vaccine ◽  
2010 ◽  
Vol 28 (30) ◽  
pp. 4837-4841 ◽  
Author(s):  
Alessandra Handisurya ◽  
Christina Schellenbacher ◽  
Bärbel Reininger ◽  
Frieder Koszik ◽  
Philipp Vyhnanek ◽  
...  

2011 ◽  
Vol 208 (9) ◽  
pp. 1863-1874 ◽  
Author(s):  
Julius A. Potian ◽  
Wasiulla Rafi ◽  
Kamlesh Bhatt ◽  
Amanda McBride ◽  
William C. Gause ◽  
...  

Tuberculosis and helminthic infections coexist in many parts of the world, yet the impact of helminth-elicited Th2 responses on the ability of the host to control Mycobacterium tuberculosis (Mtb) infection has not been fully explored. We show that mice infected with the intestinal helminth Nippostrongylus brasiliensis (Nb) exhibit a transitory impairment of resistance to airborne Mtb infection. Furthermore, a second dose of Nb infection substantially increases the bacterial burden in the lungs of co-infected mice. Interestingly, the Th2 response in the co-infected animals did not impair the onset and development of the protective Mtb-specific Th1 cellular immune responses. However, the helminth-induced Th2 environment resulted in the accumulation of alternatively activated macrophages (AAMs) in the lung. Co-infected mice lacking interleukin (IL) 4Rα exhibited improved ability to control Mtb infection, which was accompanied by significantly reduced accumulation of AAMs. Moreover, IL-4Rα−/− mice adoptively transferred with wild-type macrophages had a significantly higher Mtb load in their lungs compared with those that received IL-4Rα−/− macrophages, suggesting a direct contribution for the IL-4R pathway to the heightened susceptibility of co-infected animals. The Th2 response can thus enhance the intracellular persistence of Mtb, in part by mediating the alternative activation of macrophages via the IL-4Rα signaling pathway.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Youngwoo Cho ◽  
Saeyoull Cho

AbstractIn this study, more than 1,000 cricket (Gryllus bimaculatus) hemocytes were classified based on their size and morphology. These hemocytes were classified into six types: granulocytes, plasmatocytes, prohemocytes, spherulocytes, coagulocytes, and oenocytoids. Hemocyte cultures was observed in real time to determine which hemocytes were associated with cellular immune responses against potential pathogens. Granulocytes were identified as the professional immune cell that mediates nodulation, encapsulation, and phagocytosis of pathogens. Granulocytes have been shown to actively produce various sticky nets (amoeba-like hairs and extracellular traps) from their plasma membranes that they use to gather other hemocytes and to implement cellular immune responses. The activation of lysosomes in granulocytes started at 4 h, peaked at 12 h, and returned to baseline by 24 h post-infection. At 48 h post-infection, cells could be found within the cytoplasm of granulocytes and reactivated lysosomes surrounding these cells were visible. This result seems to reflect a phenomenon in which necrotic granulocytes are removed by other healthy granulocytes. This unique mechanism of cellular immunity is therefore a way to efficiently and effectively remove pathogens and simultaneously maintain healthy hemocytes.


1975 ◽  
Vol 142 (4) ◽  
pp. 839-855 ◽  
Author(s):  
R M Bhatnagar ◽  
J B Zabriskie ◽  
A R Rausen

Several in vitro parameters of cellular immunity were examined in BALB/c mice with an experimentally induced fibrosarcoma tumor. The results of capillary migration of spleen cells in high tumor cell dose inoculated mice show appearance of cellular immune response in the early stages of the tumor growth. As the tumor progresses, the cellular response declines and rapidly disappears, culminating in stimulation values near the time of the death of these mice. The blastogenic studies also show early cellular recognition of tumor antigen by mouse spleen cells and whole blood (Z24 h). After the 2nd day following tumor injection, no blast transformation is noted. However, the results obtained with a lower inoculating tumor cell dose demonstrate an initial cellular recognition on the 7th day. This response gradually disappears by the 19th day and remains negative up to the time of the death of these mice. This cellular immunity was confirmed by the cytotoxic experiments showing that the primary cells responsible for this cellular reactivity were the immune cells. An interesting finding was the presence of a factor(s) capable of blocking the cytotoxic effect. The nature and mechanism of this blocking factor(s) is now under investigation.


2015 ◽  
Vol 55 (3) ◽  
pp. 287-293 ◽  
Author(s):  
Seyyedeh Kimia Mirhaghparast ◽  
Arash Zibaee ◽  
Hassan Hoda ◽  
Jalal Jalali Sendi

Abstract The effects of pyriproxyfen were determined on the cellular immunity and phenoloxidase activity in the 4th instar larvae of Chilo suppressalis Walker. The bioassay results revealed the effective concentrations of: 10L : 18C, 30L : 72C and 50L : 190C μg · ml−1. The sole effect of 18 and 72 μg · ml−1 concentrations at intervals of 1–3 h caused a higher number of total hemocytes in the treated larvae than the control, but the reverse results were observed after 6–24 h. The number of plasmatocytes was lower than that of the control for intervals of 3–24 h but the number of granulocytes was higher than the control after 1–3 h although no significant differences were observed at the other times. In the treated larvae, the activities of phenoloxidase were higher and lower than those of the control after 1–3 h and 6–24 h, respectively. The combined effects of pyriproxyfen and the entomopathogenic fungus, Beauveria bassiana isolate B3 caused higher numbers of total hemocytes, plasmatocytes, and granulocytes in the treated larvae by use of the three concentrations of pyriproxyfen, at intervals of 6 and 12 h. Although the numbers of nodules in the larvae treated with concentrations of 18 μg · ml−1 were higher than those of other treatments, the overall numbers were lower than those of the control. Finally, the activity of phenoloxidase in the treated larvae was higher than that of the control, at intervals of 6 and 12 h post-treatment. Findings of the current study indicate an intervening role of pyriproxyfen in the cellular immunity of C. suppressalis to entomopathogenic objects.


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