scholarly journals A Glimpse into the Diverse Cellular Immunity against SARS-CoV-2

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 827
Author(s):  
Cheng-Wei Chang ◽  
Yuchen Liu ◽  
Cheng Jiao ◽  
Hongwei Liu ◽  
Jie Gong ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cellular Immunity ◽  
Critical Role ◽  
Wild Type Virus ◽  
T Cell Epitopes ◽  
Type Virus ◽  
Healthy Individuals ◽  
Wild Type ◽  
Cellular Immune

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response has been shown to play a critical role in preventing severe illness or death in patients infected with SARS-CoV-2 or its variants. Given the multiple T-cell epitopes shared by wild-type virus and its variants, we hypothesized that vaccines that target multiple T-cell epitopes of SARS-CoV-2 may provide a “universal protection” against the wild-type virus as well as its variants, even the heavily mutated ones. To test this, we assessed SARS-CoV-2-specific T-cell precursors in healthy individuals using overlapping peptide pools of SARS-CoV-2 structural and functional proteins, including spike (S), membrane (M), envelope (E), nucleocapsid (N), and protease (P) proteins as target antigens. Diverse T-cell precursor frequencies specific to these viral antigens were detected in healthy individuals, including high, medium, low, and no responders. This was further confirmed by efficient induction of anti-SARS-CoV-2 T-cell immune responses using ex vivo dendritic cell (DC)/T cell coculture. The results demonstrated T-cell responses consistent with the precursor frequencies of each of the individuals tested. Importantly, the combination of all five viral peptide pools induced the strongest cellular immune response, and further, after a DC-peptides re-stimulation, even the no responders developed an increased anti-viral T-cell response. These analyses recapitulate the presence of a broad anti-SARS-CoV-2 cellular immunity even in an immune naïve population, which could be enhanced by antigen presenting cells presenting the overlapping antigenic peptides. Given the critical role of cellular immunity in COVID-19 protection, these results have important implications for vaccine design and immunotherapy in fighting SARS-CoV-2 and its variants.

scholarly journals A glimpse into the diverse cellular immunity against SARS-CoV-2 

2020 ◽  
Author(s):  
Lung-Ji Chang ◽  
Cheng-Wei Chang ◽  
Yuchen Liu ◽  
Cheng Jiao ◽  
Hongwei Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Cellular Immune Response ◽  
Critical Role ◽  
T Cell Response ◽  
Viral Antigens ◽  
Cellular Immune

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response may prove to be essential for long-term immune protection against the novel coronavirus disease 2019 (COVID-19). To assess COVID-19-specific immunity in the population, we synthesized selected peptide pools of SARS-CoV-2 structural and functional proteins, including Spike (S), Membrane (M), envelope (E), Nucleocapsid (N) and Protease (P) as target antigens. Survey of the T cell precursur frequencies in healthy individuals specific to these viral antigens demonstrated a diverse cellular immunity, including high, medium, low and no responders. This was further confirmed by in vitro induction of anti-SARS-CoV-2 T cell immune responses using dendritic cell (DC)/T cell coculture, which was consistent with the corresponding T cell precursor frequencies in each individual tested. In general, the combination of all five antigenic pools induced the strongest cellular immune response, and individual donors responded differently to different viral antigens. Importantly, a secondary in vitro booster stimulation of the T cells with the DC-peptides induced increased anti-viral immune responses in all individuals even in the no responders, suggesting that booster immunization in a vaccine scheme may elicit a broad protection in immune naïve population. Our analysis illustrates the critical role of cellular immunity in fighting COVID-19 and the importance of analyzing anti-SARS-CoV-2 T cell response in addition to antibody response in the population.

scholarly journals Directed attenuation to enhance vaccine immunity

2021 ◽  
Vol 17 (2) ◽  
pp. e1008602
Author(s):  
Rustom Antia ◽  
Hasan Ahmed ◽  
James J. Bull
Keyword(s):  
Immune Response ◽  
Genetic Engineering ◽  
Adaptive Immunity ◽  
Immune Evasion ◽  
Viral Infections ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Innate And Adaptive Immunity ◽  
Live Attenuated Vaccines

Many viral infections can be prevented by immunizing with live, attenuated vaccines. Early methods of attenuation were hit-and-miss, now much improved by genetic engineering. However, even current methods operate on the principle of genetic harm, reducing the virus’s ability to grow. Reduced viral growth has the undesired side-effect of reducing the host immune response below that of infection with wild-type. Might some methods of attenuation instead lead to an increased immune response? We use mathematical models of the dynamics of virus with innate and adaptive immunity to explore the tradeoff between attenuation of virus pathology and immunity. We find that modification of some virus immune-evasion pathways can indeed reduce pathology yet enhance immunity. Thus, attenuated vaccines can, in principle, be directed to be safe yet create better immunity than is elicited by the wild-type virus.

scholarly journals The Poxvirus A35 Protein Is an Immunoregulator

2009 ◽  
Vol 84 (1) ◽  
pp. 418-425 ◽  
Author(s):  
Kristina E. Rehm ◽  
Gwendolyn J. B. Jones ◽  
Alice A. Tripp ◽  
Mark W. Metcalf ◽  
Rachel L. Roper
Keyword(s):  
Immune Response ◽  
Cytotoxic T Lymphocyte ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Lethal Challenge ◽  
Target Organs ◽  
Important Virulence Factor ◽  
Virus Mutant ◽  
Lymphocyte Responses

ABSTRACT It was shown previously that the highly conserved vaccinia virus A35 gene is an important virulence factor in respiratory infection of mice. We show here that A35 is also required for full virulence by the intraperitoneal route of infection. A virus mutant in which the A35 gene has been removed replicated normally and elicited improved antibody, gamma interferon-secreting cell, and cytotoxic T-lymphocyte responses compared to wild-type virus, suggesting that A35 increases poxvirus virulence by immunomodulation. The enhanced immune response correlated with an improved control of viral titers in target organs after the development of the specific immune response. Finally, the A35 deletion mutant virus also provided protection from lethal challenge (1,000 50% lethal doses) equal to that of the wild-type virus. Together, these data suggest that A35 deletion viruses will make safer and more efficacious vaccines for poxviruses. In addition, the A35 deletion viruses will serve as improved platform vectors for other infectious diseases and cancer and will be superior vaccine choices for postexposure poxvirus vaccination, as they also provide improved kinetics of the immune response.

scholarly journals T-Cell-Line-Tropic Human Immunodeficiency Virus Type 1 That Is Made Resistant to Stromal Cell-Derived Factor 1α Contains Mutations in the Envelope gp120 but Does Not Show a Switch in Coreceptor Use

1998 ◽  
Vol 72 (5) ◽  
pp. 4032-4037 ◽  
Author(s):  
Dominique Schols ◽  
José A. Esté ◽  
Cecilia Cabrera ◽  
Erik De Clercq
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Stromal Cell ◽  
Wild Type Virus ◽  
Type Virus ◽  
Resistant Virus ◽  
Wild Type ◽  
Immunodeficiency Virus ◽  
Stromal Cell Derived Factor

ABSTRACT The NL4.3 T-cell-line-tropic human immunodeficiency virus type 1 strain is sensitive to the CXC chemokine stromal cell-derived factor 1α (SDF-1α), the natural ligand for CXC chemokine receptor 4 (CXCR4); the 50% inhibitory concentration (IC50) in MT-4 cells is 130 ng/ml. We generated resistant virus through passaging of the virus in the presence of increasing concentrations of SDF-1α. After 24 passages, the virus was no longer sensitive to SDF-1α (SDF-1αres virus) (IC50, >2 μg/ml) and became resistant to SDF-1β (IC50, >2 μg/ml) and to a specific CXCR4 monoclonal antibody (IC50, >20 μg/ml). The SDF-1αres virus was about 10-fold less sensitive than the wild-type virus to the bicyclam AMD3100, a specific CXCR4 antagonist. The SDF-1αres virus contained the following mutations in the gp120 molecule: N106K in the V1 loop; S134N and F145L in the V2 loop; F245I in the C2 loop; K269E, Q278H, I288V, and N293D in the V3 loop; a deletion of 5 amino acids (FNSTW) at positions 364 to 368 in the V4 loop; and R378T in the CD4 binding domain. Replication of the NL4.3 wild-type virus and the SDF-1αres virus was demonstrated in U87 cells that coexpressed CD4 and CXCR4 (U87.CD4.CXCR4) but not in U87.CD4.CCR5 cells. Thus, the resistant virus was not able to switch to the CC chemokine receptor 5 (CCR5) coreceptor (the main coreceptor for macrophage-tropic viruses). The SDF-1αres virus replicated in HOS.CD4 cells expressing CCR1, CCR2b, CCR3, CCR4, CCR5, and CXCR4 but also in HOS.CD4.pBABE cells. However, all HOS transfectant cells expressed a low level of CXCR4. Neither of the two virus strains was able to infect HOS.CXCR4 or HOS.CCR5 transfectants, demonstrating the necessity of the CD4 receptor. The T-cell-line-tropic SDF-1αres virus was thus able to overcome the inhibitory effect of SDF-1α through mutations in gp120 but still needed CXCR4 to enter the cells.

scholarly journals Plant Hsp90 is a novel adjuvant that elicits a strong humoral and cellular immune response against B- and T-cell epitopes of a Toxoplasma gondii SAG1 peptide

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Edwin F. Sánchez-López ◽  
Mariana G. Corigliano ◽  
Romina M. Albarracín ◽  
Valeria A. Sander ◽  
Ariel Legarralde ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Toxoplasma Gondii ◽  
Cellular Immune Response ◽  
T Cell Epitopes ◽  
Cellular Immune

scholarly journals Immunization by Replication-Competent Controlled Herpesvirus Vectors

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
David C. Bloom ◽  
Robert K. Tran ◽  
Joyce Feller ◽  
Richard Voellmy
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Viral Vectors ◽  
Wild Type Virus ◽  
Wild Type ◽  
Equine Influenza Virus ◽  
Heterologous Antigen ◽  
Equine Influenza ◽  
Cellular Immune ◽  
Gene Switch

ABSTRACT Replication-competent controlled virus vectors were derived from the virulent herpes simplex virus 1 (HSV-1) wild-type strain 17syn+ by placing one or two replication-essential genes under the stringent control of a gene switch that is coactivated by heat and an antiprogestin. Upon activation of the gene switch, the vectors replicate in infected cells with an efficacy that approaches that of the wild-type virus from which they were derived. Essentially no replication occurs in the absence of activation. When administered to mice, localized application of a transient heat treatment in the presence of systemic antiprogestin results in efficient but limited virus replication at the site of administration. The immunogenicity of these viral vectors was tested in a mouse footpad lethal challenge model. Unactivated viral vectors—which may be regarded as equivalents of inactivated vaccines—induced detectable protection against lethality caused by wild-type virus challenge. Single activation of the viral vectors at the site of administration (rear footpads) greatly enhanced protective immune responses, and a second immunization resulted in complete protection. Once activated, vectors also induced far better neutralizing antibody and HSV-1-specific cellular immune responses than unactivated vectors. To find out whether the immunogenicity of a heterologous antigen was also enhanced in the context of efficient transient vector replication, a virus vector constitutively expressing an equine influenza virus hemagglutinin was constructed. Immunization of mice with this recombinant induced detectable antibody-mediated neutralization of equine influenza virus, as well as a hemagglutinin-specific cellular immune response. Single activation of viral replication resulted in a severalfold enhancement of these immune responses. IMPORTANCE We hypothesized that vigorous replication of a pathogen may be critical for eliciting the most potent and balanced immune response against it. Hence, attenuation/inactivation (as in conventional vaccines) should be avoided. Instead, the necessary safety should be provided by placing replication of the pathogen under stringent control and by activating time-limited replication of the pathogen strictly in an administration region in which pathology cannot develop. Immunization will then occur in the context of highly efficient pathogen replication and uncompromised safety. We found that localized activation in mice of efficient but limited replication of a replication-competent controlled herpesvirus vector resulted in a greatly enhanced immune response to the virus or an expressed heterologous antigen. This finding supports the above-mentioned hypothesis and suggests that the vectors may be promising novel agents worth exploring for the prevention/mitigation of infectious diseases for which efficient vaccination is lacking, in particular in immunocompromised patients.

scholarly journals Infection with Cytotoxic T-Lymphocyte Escape Mutants Results in Increased Mortality and Growth Retardation in Mice Infected with a Neurotropic Coronavirus

1998 ◽  
Vol 72 (7) ◽  
pp. 5912-5918 ◽  
Author(s):  
Lecia Pewe ◽  
Shurong Xue ◽  
Stanley Perlman
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cd8 T Cell ◽  
Clinical Disease ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Escape Mutants ◽  
Ctl Escape

ABSTRACT C57BL/6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis several weeks after inoculation. Previously, we showed that mutations in the immunodominant CD8 T-cell epitope (S-510-518) could be detected in nearly all samples of RNA and virus isolated from these mice. These mutations abrogated recognition by T cells harvested from the central nervous systems of infected mice in direct ex vivo cytotoxicity assays. These results suggested that cytotoxic T-lymphocyte (CTL) escape mutants contributed to virus amplification and the development of clinical disease in mice infected with wild-type virus. In the present study, the importance of these mutations was further evaluated by infecting naive mice with MHV-JHM variants isolated from infected mice and in which epitope S-510-518 was mutated. Compared to mice infected with wild-type virus, variant virus-infected animals showed higher mortality and morbidity manifested by decreased weight gain and neurological signs. Although a delay in the kinetics of virus clearance has been demonstrated in previous studies of CTL escape mutants, this is the first illustration of significant changes in clinical disease resulting from infection with viruses able to evade the CD8 T-cell immune response.

scholarly journals Vaccine-Induced T Cells Control Reversion of AIDS Virus Immune Escape Mutants

2007 ◽  
Vol 81 (8) ◽  
pp. 4137-4144 ◽  
Author(s):  
Caroline S. Fernandez ◽  
Miranda Z. Smith ◽  
C. Jane Batten ◽  
Robert De Rose ◽  
Jeanette C. Reece ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Acute Infection ◽  
T Cell Response ◽  
Mutant Virus ◽  
Wild Type Virus ◽  
Escape Mutant ◽  
Type Virus ◽  
Wild Type ◽  
Hiv Vaccines

ABSTRACT Many current-generation human immunodeficiency virus (HIV) vaccines induce specific T cells to control acute viremia, but their utility following infection with escape mutant virus is unclear. We studied reversion to wild type of an escape mutant simian-HIV in major histocompatibility complex-matched vaccinated pigtail macaques. High levels of vaccine-induced CD8+ T cells strongly correlated with maintenance of escape mutant virus during acute infection. Interestingly, in animals with lower CD8+ T-cell levels, transient reversion to wild-type virus resulted in better postacute control of viremia. Killing of wild-type virus facilitated by transient reversion outweighs the benefit of a larger CD8+ T-cell response that only maintains the less fit escape mutant virus. These findings have important implications for the further development of T-cell-based HIV vaccines where exposure to escape mutant viruses is common.

Sign in / Sign up

Export Citation Format

Share Document