scholarly journals Characterization and immunological analysis of the rhesus cytomegalovirus homologue (Rh112) of the human cytomegalovirus UL83 lower matrix phosphoprotein (pp65)

2006 ◽  
Vol 87 (4) ◽  
pp. 777-787 ◽  
Author(s):  
Yujuan Yue ◽  
Amitinder Kaur ◽  
Shan Shan Zhou ◽  
Peter A. Barry
Keyword(s):  
Immune Responses ◽  
Human Cytomegalovirus ◽  
Rhesus Macaques ◽  
Open Reading Frames ◽  
Cross Sectional ◽  
Host Immune Responses ◽  
Macaque Model ◽  
Cell Responses ◽  
Rhesus Cytomegalovirus ◽  
Humoral Responses

Rhesus cytomegalovirus (RhCMV) contains two open reading frames (Rh111 and Rh112) that encode proteins homologous to the phosphoprotein 65 (pp65) of the human cytomegalovirus (HCMV) UL83 gene. As HCMV pp65 elicits protective immune responses in infected humans and represents an important vaccination target, one RhCMV homologue of HCMV pp65, pp65-2 (Rh112), was characterized and analysed for its ability to induce host immune responses. Similar to its HCMV counterpart, RhCMV pp65-2 was expressed as a late gene, localized to the nucleus within pp65-2-expressing cells and was present within infectious virions. Longitudinal and cross-sectional studies of pp65-2 immunity in naturally infected rhesus macaques showed that humoral responses to pp65-2 were elicited early during infection, but were not always sustained over time. In contrast, pp65-2-specific T-cell responses, examined by gamma interferon ELISPOT, were broadly detectable in all of the animals studied during primary infection and persisted in the vast majority of RhCMV-seropositive monkeys. Moreover, there was considerable inter-animal variability in the pattern of the immune responses to pp65-2. Together, these results demonstrated that RhCMV pp65-2 exhibited biological and immunological homology to HCMV pp65. Thus, the rhesus macaque model of HCMV persistence and pathogenesis should be relevant for addressing pp65-based vaccine modalities.

scholarly journals Neutralization of rhesus cytomegalovirus IL-10 reduces horizontal transmission and alters long-term immunity

2019 ◽  
Vol 116 (26) ◽  
pp. 13036-13041 ◽  
Author(s):  
Jesse D. Deere ◽  
W. L. William Chang ◽  
Andradi Villalobos ◽  
Kimberli A. Schmidt ◽  
Ashlesha Deshpande ◽  
...  
Keyword(s):  
Immune Responses ◽  
Persistent Infection ◽  
Vaccine Development ◽  
Rhesus Macaques ◽  
Horizontal Transmission ◽  
Severe Disease ◽  
Interleukin 10 ◽  
Primate Model ◽  
Host Immune Responses ◽  
Rhesus Cytomegalovirus

Human cytomegalovirus (HCMV) causes severe disease in infants and immunocompromised people. There is no approved HCMV vaccine, and vaccine development strategies are complicated by evidence of both persistent infection and reinfection of people with prior immunity. The greatest emphasis has been placed on reducing transmission to seronegative pregnant women to prevent vertical transmission and its potentially severe sequelae. Increasing evidence suggests that the earliest host–HCMV interactions establish conditions for viral persistence, including evasion of host immune responses to the virus. Using a nonhuman primate model of HCMV infection, we show that rhesus macaques immunized against viral interleukin-10 (IL-10) manifest delayed rhesus cytomegalovirus (RhCMV) acquisition and altered immune responses to the infection when it does occur. Among animals with the greatest antiviral IL-10–neutralizing activity, the timing of RhCMV seroconversion was delayed by an average of 12 weeks. After acquisition, such animals displayed an antibody response to the new infection, which peaked as expected after 2 weeks but then declined rapidly. In contrast, surprisingly, vaccination with glycoprotein B (gB) protein had no discernible impact on these outcomes. Our results demonstrate that viral IL-10 is a key regulator of successful host immune responses to RhCMV. Viral IL-10 is, therefore, an important target for vaccine strategies against cytomegalovirus (CMV). Furthermore, given the immunoregulatory function of viral IL-10, targeting this protein may prove synergistic with other vaccine therapies and targets. Our study also provides additional evidence that the earliest host–CMV interactions can have a significant impact on the nature of persistent infection.

scholarly journals Human Cytomegalovirus-Encoded microRNAs Can Be Found in Saliva Samples from Renal Transplant Recipients

2020 ◽  
Vol 6 (4) ◽  
pp. 50
Author(s):  
Shelley Waters ◽  
Silvia Lee ◽  
Kylie Munyard ◽  
Ashley Irish ◽  
Patricia Price ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Immune Responses ◽  
Human Cytomegalovirus ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Host Immune Responses ◽  
Cell Responses ◽  
Hcmv Disease ◽  
Mirna Species

Human cytomegalovirus (HCMV) infections are common following renal transplantation and may have long-lasting effects. HCMV can be measured directly by viral DNA or indirectly via host immune responses. HCMV-encoded microRNA (miRNA) may alter the pathobiology of HCMV infections and contribute to the progression of HCMV disease. HCMV-encoded miRNAs can be detected in blood but have not been sought in saliva. We investigated saliva samples from 32 renal transplant recipients (RTR) and 12 seropositive healthy controls for whom immunological data was available. Five HCMV-encoded miRNAs (miR-UL112-5p, miR-US5-2-3p, miR-UL36, miR-US25-2-3p and miR-UL22A) were sought using primer probe assays. HCMV miRNA species were detected in saliva from 15 RTR and 3 healthy controls, with miR-US5-2-3p most commonly detected. The presence of HCMV miRNAs associated with increased T-cell responses to HCMV IE-1 in RTR, suggesting a link with frequent reactivations of HCMV.

scholarly journals Host Immune Responses to a Viral Immune Modulating Protein: Immunogenicity of Viral Interleukin-10 in Rhesus Cytomegalovirus-Infected Rhesus Macaques

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e37931 ◽  
Author(s):  
Meghan K. Eberhardt ◽  
W. L. William Chang ◽  
Naomi J. Logsdon ◽  
Yujuan Yue ◽  
Mark R. Walter ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rhesus Macaques ◽  
Interleukin 10 ◽  
Host Immune Responses ◽  
Rhesus Cytomegalovirus

scholarly journals DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge

2009 ◽  
Vol 106 (37) ◽  
pp. 15831-15836 ◽  
Author(s):  
Margherita Rosati ◽  
Cristina Bergamaschi ◽  
Antonio Valentin ◽  
Viraj Kulkarni ◽  
Rashmi Jalah ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Chronic Phase ◽  
Dna Vaccination ◽  
Effector Memory ◽  
Virus Challenge ◽  
Macaque Model ◽  
Effector Memory T Cells ◽  
Humoral Responses

Optimized plasmid DNAs encoding the majority of SIVmac239 proteins and delivered by electroporation (EP) elicited strong immune responses in rhesus macaques. Vaccination decreased viremia in both the acute and chronic phases of infection after challenge with pathogenic SIVmac251. Two groups of macaques were vaccinated with DNA plasmids producing different antigen forms, “native” and “modified,” inducing distinct immune responses. Both groups showed significantly lower viremia during the acute phase of infection, whereas the group immunized with the native antigens showed better protection during the chronic phase (1.7 log decrease in virus load, P = 0.009). Both groups developed strong cellular and humoral responses against the DNA vaccine antigens, which included Gag, Pol, Env, Nef, and Tat. Vaccination induced both central memory and effector memory T cells that were maintained at the day of challenge, suggesting the potential for rapid mobilization upon virus challenge. The group receiving the native antigens developed higher and more durable anti-Env antibodies, including neutralizing antibodies at the day of challenge. These results demonstrate that DNA vaccination in the absence of any heterologous boost can provide protection from high viremia comparable to any other vaccine modalities tested in this macaque model.

scholarly journals Genetically barcoded SIV reveals the emergence of escape mutations in multiple viral lineages during immune escape

2019 ◽  
Vol 117 (1) ◽  
pp. 494-502
Author(s):  
Taina T. Immonen ◽  
Celine Camus ◽  
Carolyn Reid ◽  
Christine M. Fennessey ◽  
Gregory Q. Del Prete ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Escape ◽  
Rhesus Macaques ◽  
Quantitative Measure ◽  
Population Level ◽  
Therapeutic Interventions ◽  
Viral Escape ◽  
Virus Population ◽  
Host Immune Responses ◽  
Immune Pressure

The rapidity of replication coupled with a high mutation rate enables HIV to evade selective pressures imposed by host immune responses. Investigating the ability of HIV to escape different selection forces has generally relied on population-level measures, such as the time to detectable escape mutations in plasma and the rate these mutations subsequently take over the virus population. Here we employed a barcoded synthetic swarm of simian immunodeficiency virus (SIV) in rhesus macaques to investigate the generation and selection of escape mutations within individual viral lineages at the Mamu-A*01-restricted Tat-SL8 epitope. We observed the persistence of more than 1,000 different barcode lineages following selection after acquiring escape mutations. Furthermore, the increased resolution into the virus population afforded by barcode analysis revealed changes in the population structure of the viral quasispecies as it adapted to immune pressure. The high frequency of emergence of escape mutations in parallel viral lineages at the Tat-SL8 epitope highlights the challenge posed by viral escape for the development of T cell-based vaccines. Importantly, the level of viral replication required for generating escape mutations in individual lineages can be directly estimated using the barcoded virus, thereby identifying the level of efficacy required for a successful vaccine to limit escape. Overall, assessing the survival of barcoded viral lineages during selection provides a direct and quantitative measure of the stringency of the underlying genetic bottleneck, making it possible to predict the ability of the virus to escape selective forces induced by host immune responses as well as during therapeutic interventions.

scholarly journals Vaccine-breakthrough infection by the SARS-CoV-2 Omicron variant elicits broadly cross-reactive immune responses

2021 ◽  
Author(s):  
Runhong Zhou ◽  
Kelvin Kai-Wang To ◽  
Qiaoli Peng ◽  
Jacky Man-Chun Chan ◽  
Haode Huang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Preventive Strategies ◽  
Gamma Delta ◽  
Breakthrough Infection ◽  
Host Immune Responses ◽  
Cell Responses ◽  
Booster Vaccine ◽  
Ic50 Values ◽  
The Mean

Highly transmissible SARS-CoV-2 Omicron variant has posted a new crisis for COVID-19 pandemic control. Within a month, Omicron is dominating over Delta variant in several countries probably due to immune evasion. It remains unclear whether vaccine-induced memory responses can be recalled by Omicron infection. Here, we investigated host immune responses in the first vaccine-breakthrough case of Omicron infection in Hong Kong. We found that the breakthrough infection rapidly recruited potent cross-reactive broad neutralizing antibodies (bNAbs) against current VOCs, including Alpha, Beta, Gamma, Delta and Omicron, from unmeasurable IC50 values to mean 1:2929 at around 9-12 days, which were higher than the mean peak IC50 values of BioNTech-vaccinees. Cross-reactive spike- and nucleocapsid-specific CD4 and CD8 T cell responses were detected. Similar results were also obtained in the second vaccine-breakthrough case of Omicron infection. Our preliminary findings may have timely implications to booster vaccine optimization and preventive strategies of pandemic control.

scholarly journals Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals

2021 ◽  
Author(s):  
Marie I. Samanovic ◽  
Amber R. Cornelius ◽  
Sophie L. Gray-Gaillard ◽  
Joseph Richard Allen ◽  
Trishala Karmacharya ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Efficacy ◽  
Vaccine Dose ◽  
Prior History ◽  
Vaccine Candidates ◽  
Antibody Secreting Cell ◽  
Cell Responses ◽  
Efficacy Trials ◽  
History Of ◽  
Humoral Responses

ABSTRACTThe use of COVID-19 vaccines will play a major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccine candidates have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccine candidates differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 13 adults who recovered from COVID-19, compared to 19 adults who did not have prior COVID-19 diagnosis. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8 T cell responses in both cohorts. Furthermore, SARS-CoV-2-naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses following each dose of vaccine, whereas SARS-CoV-2-experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but muted responses to the second dose of the vaccine for the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have significant implications for personalizing mRNA vaccination regimens used to prevent COVID-19.One Sentence SummaryPrior history of COVID-19 affects adaptive immune responses to mRNA vaccination.

scholarly journals Chlamydia Lipooligosaccharide Has Varied Direct and Indirect Roles in Evading both Innate and Adaptive Host Immune Responses

2020 ◽  
Vol 88 (8) ◽  
Author(s):  
Xisheng Wang ◽  
Daniel D. Rockey ◽  
Brian P. Dolan
Keyword(s):  
Immune Responses ◽  
Cytotoxic T Cell ◽  
Innate Immune Responses ◽  
Content Type ◽  
E Coli ◽  
Host Immune Responses ◽  
Cell Responses ◽  
Direct Delivery ◽  
Cytotoxic T Cell Responses

ABSTRACT Chlamydia bacteria are obligate intracellular pathogens which can cause a variety of disease in humans and other vertebrate animals. To successfully complete its life cycle, Chlamydia must evade both intracellular innate immune responses and adaptive cytotoxic T cell responses. Here, we report on the role of the chlamydial lipooligosaccharide (LOS) in evading the immune response. Chlamydia infection is known to block the induction of apoptosis. However, when LOS synthesis was inhibited during Chlamydia trachomatis infection, HeLa cells regained susceptibility to apoptosis induction following staurosporine treatment. Additionally, the delivery of purified LOS to the cytosol of cells increased the levels of the antiapoptotic protein survivin. An increase in survivin levels was also detected following C. trachomatis infection, which was reversed by blocking LOS synthesis. Interestingly, while intracellular delivery of lipopolysaccharide (LPS) derived from Escherichia coli was toxic to cells, LOS from C. trachomatis did not induce any appreciable cell death, suggesting that it does not activate pyroptosis. Chlamydial LOS was also a poor stimulator of maturation of bone marrow-derived dendritic cells compared to E. coli LPS. Previous work from our group indicated that LOS synthesis during infection was necessary to alter host cell antigen presentation. However, direct delivery of LOS to cells in the absence of infection did not alter antigenic peptide presentation. Taken together, these data suggest that chlamydial LOS, which is remarkably conserved across the genus Chlamydia, may act both directly and indirectly to allow the pathogen to evade the innate and adaptive immune responses of the host.

scholarly journals Schistosoma mansoni Infection Impairs Antimalaria Treatment and Immune Responses of Rhesus Macaques Infected with Mosquito-Borne Plasmodium coatneyi

2012 ◽  
Vol 80 (11) ◽  
pp. 3821-3827 ◽  
Author(s):  
Amma A. Semenya ◽  
JoAnn S. Sullivan ◽  
John W. Barnwell ◽  
W. Evan Secor
Keyword(s):  
Immune Responses ◽  
Schistosoma Mansoni ◽  
Malaria Infection ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
Content Type ◽  
Macaque Model ◽  
Malaria Parasitemia ◽  
Intravenous Inoculation ◽  
Plasmodium Coatneyi

ABSTRACTMalaria and schistosomiasis are the world's two most important parasitic infections in terms of distribution, morbidity, and mortality. In areas wherePlasmodiumandSchistosomaspecies are both endemic, coinfections are commonplace. Mouse models demonstrate that schistosomiasis worsens a malaria infection; however, just as mice and humans differ greatly, the murine-infectingPlasmodiumspecies differ as much from those that infect humans. Research into human coinfections (Schistosoma haematobium-Plasmodium falciparumversusSchistosoma mansoni-P. falciparum) has produced conflicting results. The rhesus macaque model provides a helpful tool for understanding the role ofS. mansonion malaria parasitemia and antimalarial immune responses usingPlasmodium coatneyi, a malaria species that closely resemblesP. falciparuminfection in humans. Eight rhesus macaques were exposed toS. mansonicercariae. Eight weeks later, these animals plus 8 additional macaques were exposed to malaria either through bites of infected mosquitos or intravenous inoculation. When malaria infection was initiated from mosquito bites, coinfected animals displayed increased malaria parasitemia, decreased hematocrit levels, and suppressed malaria-specific antibody responses compared to those of malaria infection alone. However, macaques infected by intravenous inoculation with erythrocytic-stage parasites did not display these same differences in parasitemia, hematocrit, or antibody responses between the two groups. Use of the macaque model provides information that begins to unravel differences in pathological and immunological outcomes observed between humans withP. falciparumthat are coinfected withS. mansoniorS. haematobium. Our results suggest that migration of malaria parasites through livers harboring schistosome eggs may alter host immune responses and infection outcomes.

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