scholarly journals Modulation of the Immune Response to the Severe Acute Respiratory Syndrome Spike Glycoprotein by Gene-Based and Inactivated Virus Immunization

2005 ◽  
Vol 79 (22) ◽  
pp. 13915-13923 ◽  
Author(s):  
Wing-pui Kong ◽  
Ling Xu ◽  
Konrad Stadler ◽  
Jeffrey B. Ulmer ◽  
Sergio Abrignani ◽  
...  

ABSTRACT Although the initial isolates of the severe acute respiratory syndrome (SARS) coronavirus (CoV) are sensitive to neutralization by antibodies through their spike (S) glycoprotein, variants of S have since been identified that are resistant to such inhibition. Optimal vaccine strategies would therefore make use of additional determinants of immune recognition, either through cellular or expanded, cross-reactive humoral immunity. Here, the cellular and humoral immune responses elicited by different combinations of gene-based and inactivated viral particles with various adjuvants have been assessed. The T-cell response was altered by different prime-boost immunizations, with the optimal CD8 immunity induced by DNA priming and replication-defective adenoviral vector boosting. The humoral immune response was enhanced most effectively through the use of inactivated virus with adjuvants, either MF59 or alum, and was associated with stimulation of the CD4 but not the CD8 response. The use of inactivated SARS virus with MF59 enhanced the CD4 and antibody response even after gene-based vaccination. Because both cellular and humoral immune responses are generated by gene-based vaccination and inactivated viral boosting, this strategy may prove useful in the generation of SARS-CoV vaccines.

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
S. D. Perera ◽  
S. S. N. Perera

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.


1999 ◽  
Vol 41 (2) ◽  
pp. 107-114 ◽  
Author(s):  
J. MEGID ◽  
M.T.S. PERAÇOLI ◽  
P.R. CURI ◽  
C.R. ZANETTI ◽  
W.H. CABRERA ◽  
...  

The cellular and humoral immune responses of mice inoculated with rabies virus and treated with the Bacillus of Calmette-Guérin, Avridine and Propionibacterium acnes were evaluated in this paper. There was a higher percentage of surviving mice in groups submitted to P. acnes treatment. Lower levels of interferon-<FONT FACE="Symbol">g</font> (IFN-<FONT FACE="Symbol">g</font>) were found in infected mice. The intra-pad inoculation test (IPI) was not effective to detect cellular immune response, contrary to the results found in MIF reaction. The survival of mice did not present correlation with the levels of antirabies serum neutralizing (SN) antibodies titers, IFN-<FONT FACE="Symbol">g</font> concentration and MIF response.


2019 ◽  
Vol 12 (07) ◽  
pp. 1950077 ◽  
Author(s):  
Sulanie Perera ◽  
S. S. N. Perera

Dengue is an acute arthropode-borne virus, belonging to the family Flaviviridae. Currently, there are no vaccines or treatments available against dengue. Thus it is important to understand the dynamics of dengue in order to control the infection. In this paper, we study the long-term dynamics of the model that is presented in [S. D. Perera and S. S. N. Perera, Simulation model for dynamics of dengue with innate and humoral immune responses, Comput. Math. Methods Med. 2018 (2018) 8798057, 18 pp. https://doi.org/10.1155/2018/8798057 ] which describes the interaction of virus with infected and uninfected cells in the presence of innate and humoral immune responses. It was found the model has three equilibria, namely: infection free equilibrium, no immune equilibrium and endemic equilibrium, then analyzed its stability analytically. The analytical findings of each model have been exemplified by numerical simulations. Given the fact that intensity of dengue virus replication at early times of infection could determine clinical outcomes, it is important to understand the impact of innate immunity, which is believed to be the first line of defense against an invading pathogen. For this we carry out a simulation case study to investigate the importance of innate immune response on dengue virus dynamics. A comparison was done assuming that innate immunity was active; innate immunity was in quasi-steady state and innate immunity was inactive during the virus replication process. By a further analysis of the qualitative behavior of the quasi-steady state, it was observed that innate immune response plays a pivotal role in dengue virus dynamics. It can change the dynamical behavior of the system and is essential for the virus clearance.


2014 ◽  
Vol 11 (6) ◽  
pp. 70-75
Author(s):  
A V Sobolev ◽  
O V Aak

Recovering from bacterial infections in the first years of life reduces further risk of allergic diseases. Effects of bacterial immunomodulator Broncho Vaxom on immune system to certain extent repeats the immune response that occurs during penetration of the pathogen in the body. Bacterial antigens orchestrate cellular and humoral immune responses, stimulate innate immunity, normalize cytokine balance, and are promising in the treatment of respiratory allergic diseases.


Parasitology ◽  
2017 ◽  
Vol 144 (9) ◽  
pp. 1191-1202 ◽  
Author(s):  
JORDANNA LUÍZA DE LIMA CELESTE ◽  
ANA PAULA VENUTO MOURA ◽  
JOÃO CARLOS FRANÇA-SILVA ◽  
GABRIELA MATOS DE SOUSA ◽  
SORAIA OLIVEIRA SILVA ◽  
...  

SUMMARYIn South America, visceral leishmaniasis is frequently caused byLeishmania infantumand, at an unknown frequency, byLeishmania amazonensis. Therefore, mixed infections with these organisms are possible. Mixed infections might affect the clinical course, immune response, diagnosis, treatment and epidemiology of the disease. Here we describe the clinical course of mixed infections withL. amazonensisandL. infantumin a hamster model. We show that mixed infections are associated with more severe clinical disease than infection withL. amazonensisorL. infantumalone. In spleens with mixed infections,L. infantumoutcompetedL. amazonensisin the tissue, but not in culture from tissue. We found increased levels of IgG in animals infected withL. infantum.Although more than 30 bands were revealed in a Western blot, the highest immunogenicity was observed with proteins having molecular masses of 95 and 90 kDa, whereas proteins with molecular masses of lower than 50 kDa were reactive frequently with serum from hamsters infected withL. amazonensis, and proteins with molecular masses of 80 and 70 kDa were reactive only with serum from hamsters infected withL. infantum. This finding has important implications regarding the biology ofLeishmaniaand humoral immune responses to infections with these organisms.


2015 ◽  
Vol 23 (1) ◽  
pp. 2-5 ◽  
Author(s):  
Steven M. Singer

ABSTRACTFor years, studies of the immune response toGiardia lambliainfection focused on the production of IgA by infected hosts and antigenic variation by the parasite to escape destruction by this IgA. A new study by Hanevik and colleagues (C. S. Saghaug, S. Sørnes, D. Peirasmaki, S. Svärd, N. Langeland, and K. Hanevik, Clin Vaccine Immunol 23:11–18, 2016,http://dx.doi.org/10.1128/CVI.00419-15) highlights the emerging role of interleukin-17 (IL-17) in immunity to this parasite. Along with recent studies ofGiardiainfections of animals, this work shows that IL-17 appears to be essential for the control of these infections and to be a key factor linking cellular and humoral immune responses.


2006 ◽  
Vol 203 (3) ◽  
pp. 529-539 ◽  
Author(s):  
Rika Draenert ◽  
Todd M. Allen ◽  
Yang Liu ◽  
Terri Wrin ◽  
Colombe Chappey ◽  
...  

The predictability of virus–host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape.


2021 ◽  
Vol 11 ◽  
Author(s):  
Tone Otterhaug ◽  
Sylvia Janetzki ◽  
Marij J. P. Welters ◽  
Monika Håkerud ◽  
Anne Grete Nedberg ◽  
...  

Background and AimsPhotochemical internalization (PCI) is a technology for inducing release of endocytosed antigens into the cell cytosol via a light-induced process. Preclinical experiments have shown that PCI improves MHC class I antigen presentation, resulting in strongly enhanced CD8+ T-cell responses to polypeptide antigens. In PCI vaccination a mixture of the photosensitizing compound fimaporfin, vaccine antigens, and an adjuvant is administered intradermally followed by illumination of the vaccination site. This work describes an open label, phase I study in healthy volunteers, to assess the safety, tolerability, and immune response to PCI vaccination in combination with the adjuvant poly-ICLC (Hiltonol) (ClinicalTrials.gov Identifier: NCT02947854).MethodsThe primary objective of the study was to assess the safety and local tolerance of PCI mediated vaccination, and to identify a safe fimaporfin dose for later clinical studies. A secondary objective was to analyze the immunological responses to the vaccination. Each subject received 3 doses of HPV16 E7 peptide antigens and two doses of Keyhole Limpet Hemocyanin (KLH) protein. A control group received Hiltonol and vaccine antigens only, whereas the PCI groups in addition received fimaporfin + light. Local and systemic adverse effects were assessed by standard criteria, and cellular and humoral immune responses were analyzed by ELISpot, flow cytometry, and ELISA assays.Results96 healthy volunteers were vaccinated with fimaporfin doses of 0.75–50 µg. Doses below 17.5 µg were safe and tolerable, higher doses exhibited local tolerability issues in some study subjects, mainly erythema, and pain during illumination. There were few, and only mild and expected systemic adverse events. The employment of PCI increased the number of subjects exhibiting a T-cell response to the HPV peptide vaccine about 10-fold over what was achieved with the antigen/Hiltonol combination without PCI. Moreover, the use of PCI seemed to result in a more consistent and multifunctional CD8+ T-cell response. An enhancement of the humoral immune response to KLH vaccination was also observed.ConclusionsUsing PCI in combination with Hiltonol for intradermal vaccination is safe at fimaporfin doses below 17.5 µg, and gives encouraging immune responses to peptide and protein based vaccination.


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