Mice Chronically Infected with Chimeric HIV Resist Peripheral and Brain Superinfection: A Model of Protective Immunity to HIV
Jennifer KelschenbachManisha SainiEran HadasChaojiang GuWei ChaoGalina BentsmanJessie P. HongTomáš HankeLeroy R. SharerMary Jane PotashDavid J. Volsky
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Keywords:
Superinfection
Adoptive Cell Transfer
Cellular immunity
Monoclonal antibody 2F5 recognizing the ELDKWA epitope on HIV-1 gp41 has a significant neutralization potency against 90% of the investigated viruses of African, Asian, American, and European strains, but the antibody responses to the epitope 2F5 in HIV-1-infected individuals were very low. We attempted to induce high levels of epitope-specific antibodies to ELDKWA and its three mutated epitopes by candidate epitope vaccines. The four candidate epitope vaccines all induced strong antibody responses at dilutions from about 1:6,400 to 1:25,600. We tested the cross-reactions between these antisera and four epitope peptides. The ELDKWA-specific antisera showed strong cross-reactivity with three neutralizing-resistant mutated epitopes which contain changes in the D or K positions of the epitope sequence. Virus variants containing these changes could escape neutralization by monoclonal antibody 2F5. In immunoblotting analysis, the ELDKWA, ELDEWA, and ELEKWA epitope specific antibodies all recognized rsgp41 which confirms that the antibodies against both mutated epitopes, ELDEWA and ELEKWA, could cross-react with the native epitope on rsgp41. Although it is not clear whether the polyclonal antibodies induced by the ELDKWA epitope vaccine could neutralize the mutated viruses containing these mutated epitopes, it is conceivable that epitope vaccines based on mutated epitopes could induce strong antibody responses with predefined epitope specificity to neutralize mutated viruse containing the mutated epitope. An epitope vaccine, using different epitopes including mutated epitopes, could provide a new concept for developing a new vaccine against HIV-1.
Linear epitope
Polyclonal antibodies
Epitope mapping
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Epitope-vaccine is a newly developing vaccine which has many advantages comparied with to the traditional vaccine.The key step for designing epitope-vaccine is to screen epitopes.The epitope-screening methods include protein degration,peptide-probing scanning,epitope prediction by computer,et al.Usually,the epitope-vaccine needs combine some carriers to display immunologic activity,for example,lipid carriers,protein carriers,and adjuvant.In addition,researchers also use tandem repeat epitopes,conformational multiple antigen peptide(MAP) and epitope modifying to strengthen the immunological efficacity.The epitope-vaccine mainly contains viral epitope-vaccine,bacterial epitope-vaccine and epitope-vaccine for parasites.Although the researches on epitope-vaccine develop fast,some problems and challenges need to resolve impendingly.
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The range of reported rates of bacterial and fungal superinfections in patients with a severe course of COVID-19 is wide, suggesting a lack of standardised reporting.The rates of bacterial and fungal superinfection were assessed using predefined criteria to differentiate between infection and contamination.Overall, 117 patients admitted to the Intensive Care Unit due to severe COVID-19 were included. Overall, 55% of patients developed a superinfection and 13.6% developed a fungal superinfection (5.9% candidemia and 7.7% CAPA). The rate of ventilator-associated pneumonia was 65.2%. If superinfection was detected, the length of hospital stay was significantly longer and the mortality was especially increased if candidemia was detected. An increased risk of superinfection was observed in patients with pre-existing diabetes mellitus or chronic heart failure. The presence of immunomodulating therapy did not seem to have an impact on the frequency of superinfections.Increased awareness of high superinfection rates, fungal infections in particular, in patients suffering from severe COVID-19 is necessary.
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HIV-1 superinfection may occur at a rate similar to that of initial infection, raising concerns for HIV-1 vaccine strategies predicated on eliciting immune responses similar to those in natural infection. Because of the high rate of recombination during HIV-1 replication, studies examining only one region of the HIV-1 genome are likely to miss cases of HIV-1 superinfection. We examined HIV-1 gag sequences from 14 high-risk Kenyan women in whom superinfection was not detected in a previous study of env sequences. We detected two additional cases of HIV-1 superinfection: one intersubtype superinfection that occurred between 1046 and 1487 days postinfection (DPI) and one intrasubtype superinfection that occurred between 341 and 440 DPI. Our results suggest that studies that examine only small genome regions may lead to underestimates of the risk of superinfection, highlighting the need for more extensive studies examining multiple regions of the HIV-1 genome.
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HIV-1 superinfection occurs frequently in high-risk populations, but its clinical consequences remain poorly characterized. We undertook this study to determine the impact of HIV-1 superinfection on disease progression.In the largest prospective cohort study of superinfection to date, we compared measures of HIV-1 progression in women who acquired superinfection with those who did not. Clinical and laboratory data were collected at quarterly intervals. Linear mixed effects models were used to compare postacute viral load and CD4 T-cell counts over time in singly infected and superinfected women. Cox proportional hazards analysis was used to determine the effect of superinfection on time to clinical progression [CD4 cell count <200 cells/μl, antiretroviral therapy (ART) initiation or death].Among 144 women, 21 of whom acquired superinfection during follow-up, the rate of viral load increase was higher in superinfected than in singly infected women (P = 0.0008). In adjusted analysis, superinfected women had lower baseline viral load before superinfection (P = 0.05) and a trend for increased viral load at superinfection acquisition (P = 0.09). We also observed a borderline association of superinfection with accelerated CD4 cell count decline (P = 0.06). However, there was no significant difference in time to clinical progression events.These data suggest that superinfection is associated with accelerated progression in laboratory measures of HIV-1 disease, but has a limited impact on the occurrence of clinical events. Our observation that superinfected individuals have lower baseline viral load prior to superinfection suggests that there may be host or viral determinants of susceptibility to superinfection.
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The retroviral phenomenon of superinfection resistance defines an interference mechanism that is established after primary infection,and provides possible protection against the challenge with the same virus.A better knowledge of superinfection resistance-induced mechanisms could be useful for the development of an HIV vaccine or other antiviral strategies.Present studies suggest that the SIR based on infected cells and the immune response in vivo were concluded to be the main possible reasons for the protection against superinfection.However,so far the real mechanism in protecting patients from HIV superinfection has not been studied throughly.This paper reviews the findings and introduces the updates of superinfection with HIV infection.
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Viral Interference
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OBJECTIVE To investigate the risk factors of superinfection and improve the rational use of antibiotics. METHODS The clinical data such as age, original disease, time of hospitalization, antibiotics used and the kinds of superinfection caused in 51 cases from 500 hospitalized patients were analyzed. RESULTS Age, severity of original disease, wide use of broad-spectrum antibacterial agents are the main reasons for superinfection. CONCLUSIONS In order to reduce the occurrence of superinfection, suitable antibiotics as well as dosage regimens should be chosen for high risk patients.
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Superinfection
Antibody response
HIV vaccine
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Linear epitope
Bovine herpesvirus 1
Epitope mapping
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