scholarly journals Dynamics of Immune Responses during ExperimentalMycobacterium kansasiiInfection of Cynomolgus Monkeys(Macaca fascicularis)

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Fangui Min ◽  
Lifang He ◽  
Yinzhu Luo ◽  
Shuwu Huang ◽  
Jinchun Pan ◽  
...  

To profile the dynamic changes of immune responses forM. kansasiiinfection, 3 cynomolgus monkeys were experimentally infected withM. kansasiiby intratracheal inhalation of 1 × 106 CFU bacteria per monkey. Every 2 to 4 weeks, tuberculin skin testings (TSTs) were performed and blood samples were collected for immunoassay. Multiple cytokines in a single sample were measured by Luminex xMAP technologies. IgM and IgA were detected by double-antibody sandwich ELISA. IgG against PPD and 11M. tuberculosisproteins were detected by using of indirect ELISA. At week 16, all animals were euthanized for necropsy and histological analysis. Positivities of TSTs emerged from week 2 to 6 postinfection. Leukocyte counts and T lymphocyte subsets experienced moderate increases. Among 44 kinds of cytokines, 36 kinds of them showed increases of different dynamic types and 8 kinds of them showed no specific changes. Total IgM and IgA showed a transient increase at an early infection stage. Positivities ofM. tuberculosisspecific IgM and IgA emerged as early as week 2 postinfection. All animals showed positive IgG against PPD and negative IgG responses to 38 kDa, MPT64L, TB16.3, 16 kDa, U1, and MTB81 antigens during the infection period. IgG against ESAT-6, CFP10, CFP10-ESAT-6, Ag85b, and 14 kDa antigens reached positive levels. The IgG avidities of PPD, ESAT-6, CFP10-ESAT-6, and Ag85b were all above 50 percent. In conclusion, the data indicate thatM. kansasiiinfection in monkeys can induce positivities of TSTs, increases of multiple cytokines, and cross-reactive antibody responses toM. tuberculosisantigens.

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Akira Yano ◽  
Kaori Ito ◽  
Yoshikatsu Miwa ◽  
Yoshito Kanazawa ◽  
Akiko Chiba ◽  
...  

The reduction of brain amyloid beta (Aβ) peptides by anti-Aβantibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβpeptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβantibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβantibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42compared to Aβfibrils. The levels of serum anti-Aβantibodies and plasma Aβpeptides increased in both animals and decreased the brain Aβ40level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβantibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβpeptides and their toxic effects via clearance of Aβpeptides by generated antibodies.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1387
Author(s):  
Yukiko Otsuka ◽  
Hitomi Tsuge ◽  
Shiori Uezono ◽  
Soshi Tanabe ◽  
Maki Fujiwara ◽  
...  

For achieving retrograde gene transfer, we have so far developed two types of lentiviral vectors pseudotyped with fusion envelope glycoprotein, termed HiRet vector and NeuRet vector, consisting of distinct combinations of rabies virus and vesicular stomatitis virus glycoproteins. In the present study, we compared the patterns of retrograde transgene expression for the HiRet vs. NeuRet vectors by testing the cortical input system. These vectors were injected into the motor cortex in rats, marmosets, and macaques, and the distributions of retrograde labels were investigated in the cortex and thalamus. Our histological analysis revealed that the NeuRet vector generally exhibits a higher efficiency of retrograde gene transfer than the HiRet vector, though its capacity of retrograde transgene expression in the macaque brain is unexpectedly low, especially in terms of the intracortical connections, as compared to the rat and marmoset brains. It was also demonstrated that the NeuRet but not the HiRet vector displays sufficiently high neuron specificity and causes no marked inflammatory/immune responses at the vector injection sites in the primate (marmoset and macaque) brains. The present results indicate that the retrograde transgene efficiency of the NeuRet vector varies depending not only on the species but also on the input projections.


2021 ◽  
Author(s):  
Cian Duggan ◽  
Eleonora Moratto ◽  
Zachary Savage ◽  
Eranthika Hamilton ◽  
Hiroaki Adachi ◽  
...  

Plants employ sensor-helper pairs of NLR immune receptors to recognize pathogen effectors and activate immune responses. Yet the subcellular localization of NLRs pre- and post- activation during pathogen infection remains poorly known. Here we show that NRC4, from the 'NRC' solanaceous helper NLR family, undergoes dynamic changes in subcellular localization by shuttling to and from the plant-pathogen haustorium interface established during infection by the Irish potato famine pathogen Phytophthora infestans. Specifically, prior to activation, NRC4 accumulates at the extra-haustorial membrane (EHM), presumably to mediate response to perihaustorial effectors, that are recognized by NRC4-dependent sensor NLRs. However not all NLRs accumulate at the EHM, as the closely related helper NRC2, and the distantly related ZAR1, did not accumulate at the EHM. NRC4 required an intact N- terminal coiled coil domain to accumulate at the EHM, whereas the functionally conserved MADA motif implicated in cell death activation and membrane insertion was dispensable for this process. Strikingly, a constitutively autoactive NRC4 mutant did not accumulate at the EHM and showed punctate distribution that mainly associated with the plasma membrane, suggesting that post-activation, NRC4 probably undergoes a conformation switch to form clusters that do not preferentially associate with the EHM. When NRC4 is activated by a sensor NLR during infection however, NRC4 formed puncta mainly at the EHM and to a lesser extent at the plasma membrane. We conclude that following activation at the EHM, NRC4 may spread to other cellular membranes from its primary site of activation to trigger immune responses.


Author(s):  
Stacey Schultz-Cherry ◽  
Maureen A McGargill ◽  
Paul G Thomas ◽  
Jeremie H Estepp ◽  
Aditya H Gaur ◽  
...  

Abstract Efficacy of COVID-19 vaccines administered after COVID-19-specific monoclonal antibody is unknown, and ‘antibody interference’ might hinder immune responses leading to vaccine failure. In an IRB-approved prospective study, we found that an individual who received mRNA COVID-19 vaccination <40 days after COVID-19-specific monoclonal antibody therapy for symptomatic COVID-19 had similar post-vaccine antibody responses to SARS-CoV-2 receptor binding domain (RBD), for four important SARS-CoV-2 variants (B.1, B.1.1.7, B.1.351 and P.1), as other participants who were also vaccinated following COVID-19. Vaccination against COVID-19 shortly after COVID-19-specific monoclonal antibody can boost and expand antibody protection, questioning the need to delay vaccination in this setting.


2020 ◽  
Vol 8 (18) ◽  
pp. 1145-1145
Author(s):  
Mingxiang Huang ◽  
Yao Wang ◽  
Jing Ye ◽  
Hongqiang Da ◽  
Sufang Fang ◽  
...  

2017 ◽  
Author(s):  
Adam J. Kucharski ◽  
Justin Lessler ◽  
Derek A.T. Cummings ◽  
Steven Riley

AbstractHuman immunity influences the evolution and impact of novel influenza strains. Because individuals are infected with multiple influenza strains during their lifetime and each virus can generate a cross-reactive antibody response, it is challenging to quantify the processes that shape observed immune responses, or to reliably detect recent infection from serological samples. Using a Bayesian model of antibody dynamics at multiple timescales, we explain complex cross-reactive antibody landscapes by inferring participants’ histories of infection with serological data from cross-sectional and longitudinal studies of influenza A/H3N2 in southern China and Vietnam. We show an individual’s influenza antibody profile can be explained by a short-lived, broadly cross-reactive response that decays within a year to leave a smaller long-term response acting against a narrower range of strains. We also demonstrate that accounting for dynamic immune responses can provide a more accurate alternative to traditional definitions seroconversion for the estimation of infection attack rates. Our work provides a general model for explaining mechanisms of influenza immunity acting at multiple timescales based on contemporary serological data, and suggests a two-armed immune response to influenza infection consistent with competitive dynamics between B cell populations. This approach to analysing multiple timescales for antigenic responses could also be applied to other multi-strain pathogens such as dengue and related flaviviruses.


2021 ◽  
Vol 16 (2) ◽  
pp. 382
Author(s):  
Bin Wang ◽  
Tian-Yun Gao ◽  
Fei-Fei Huang ◽  
Yuan-Yuan Xie ◽  
Wen-Qing Wang ◽  
...  

2021 ◽  
Vol 13 (597) ◽  
pp. eabf6348
Author(s):  
Mathieu Mateo ◽  
Stéphanie Reynard ◽  
Alexandra Journeaux ◽  
Clara Germain ◽  
Jimmy Hortion ◽  
...  

A safe and protective Lassa virus vaccine is crucially needed in Western Africa to stem the recurrent outbreaks of Lassa virus infections in Nigeria and the emergence of Lassa virus in previously unaffected countries, such as Benin and Togo. Major challenges in developing a Lassa virus vaccine include the high diversity of circulating strains and their reemergence from 1 year to another. To address each of these challenges, we immunized cynomolgus monkeys with a measles virus vector expressing the Lassa virus glycoprotein and nucleoprotein of the prototypic Lassa virus strain Josiah (MeV-NP). To evaluate vaccine efficacy against heterologous strains of Lassa virus, we challenged the monkeys a month later with heterologous strains from lineage II or lineage VII, finding that the vaccine was protective against these strains. A second cohort of monkeys was challenged 1 year later with the homologous Josiah strain, finding that a single dose of MeV-NP was sufficient to protect all vaccinated monkeys. These studies demonstrate that MeV-NP can generate both long-lasting immune responses and responses that are able to protect against diverse strains of Lassa virus.


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