scholarly journals HIV-1-Based Virus-like Particles that Morphologically Resemble Mature, Infectious HIV-1 Virions

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 507 ◽  
Author(s):  
Christopher A. Gonelli ◽  
Georges Khoury ◽  
Rob J. Center ◽  
Damian F.J. Purcell
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Expression Vectors ◽  
Virus Like Particles ◽  
Cell Responses ◽  
Hiv 1

A prophylactic vaccine eliciting both broad neutralizing antibodies (bNAbs) to the HIV-1 envelope glycoprotein (Env) and strong T cell responses would be optimal for preventing HIV-1 transmissions. Replication incompetent HIV-1 virus-like particles (VLPs) offer the opportunity to present authentic-structured, virion-associated Env to elicit bNAbs, and also stimulate T cell responses. Here, we optimize our DNA vaccine plasmids as VLP expression vectors for efficient Env incorporation and budding. The original vector that was used in human trials inefficiently produced VLPs, but maximized safety by inactivating RNA genome packaging, enzyme functions that are required for integration into the host genome, and deleting accessory proteins Vif, Vpr, and Nef. These original DNA vaccine vectors generated VLPs with incomplete protease-mediated cleavage of Gag and were irregularly sized. Mutations to restore function within the defective genes revealed that several of the reverse transcriptase (RT) deletions mediated this immature phenotype. Here, we made efficient budding, protease-processed, and mature-form VLPs that resembled infectious virions by introducing alternative mutations that completely removed the RT domain, but preserved most other safety mutations. These VLPs, either expressed from DNA vectors in vivo or purified after expression in vitro, are potentially useful immunogens that can be used to elicit antibody responses that target Env on fully infectious HIV-1 virions.

scholarly journals Optimized Adenovirus-Antibody Complexes Stimulate Strong Cellular and Humoral Immune Responses against an Encoded Antigen in Naïve Mice and Those with Preexisting Immunity

2011 ◽  
Vol 19 (1) ◽  
pp. 84-95 ◽  
Author(s):  
Jin Huk Choi ◽  
Joe Dekker ◽  
Stephen C. Schafer ◽  
Jobby John ◽  
Craig E. Whitfill ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Transduction Efficiency ◽  
Virus Antibody ◽  
Cell Responses

ABSTRACTThe immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity.In vitroandin vivoassays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 1011adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND50) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND50formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P= 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND50) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND50) and humoral (0.0005 ND50) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.

scholarly journals HIV-1 Env DNA Vaccine plus Protein Boost Delivered by EP Expands B- and T-Cell Responses and Neutralizing Phenotype In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84234 ◽  
Author(s):  
Kar Muthumani ◽  
Megan C. Wise ◽  
Kate E. Broderick ◽  
Natalie Hutnick ◽  
Jonathan Goodman ◽  
...  
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
T Cell Responses ◽  
Cell Responses ◽  
Protein Boost ◽  
Hiv 1

scholarly journals In Vitro Priming Recapitulates In Vivo HIV-1 Specific T Cell Responses, Revealing Rapid Loss of Virus Reactive CD4+ T Cells in Acute HIV-1 Infection

PLoS ONE ◽  
2009 ◽  
Vol 4 (1) ◽  
pp. e4256 ◽  
Author(s):  
Rachel Lubong Sabado ◽  
Daniel G. Kavanagh ◽  
Daniel E. Kaufmann ◽  
Karlhans Fru ◽  
Ethan Babcock ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Rapid Loss ◽  
Cell Responses ◽  
Acute Hiv ◽  
Hiv 1

scholarly journals Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mauro Di Pilato ◽  
Miguel Palomino-Segura ◽  
Ernesto Mejías-Pérez ◽  
Carmen E. Gómez ◽  
Andrea Rubio-Ponce ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Adaptive Immune System ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Adaptive Immune

AbstractNeutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. Nα and Nβ neutrophils have been described with distinct in vitro capacity to generate antigen-specific CD8 T-cell responses. However, how these cell types exert their role in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses are not known. In this study, we find that these neutrophil subtypes show distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. Moreover, after analysis of adhesion, inflammatory, and migration markers, we observe that Nβ neutrophils overexpress the α4β1 integrin compared to Nα. Finally, by inhibiting α4β1 integrin, we increase the Nβ/Nα ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system and their relevance in vaccine design.

scholarly journals Use of an In Vivo FTA Assay to Assess the Magnitude, Functional Avidity and Epitope Variant Cross-Reactivity of T Cell Responses Following HIV-1 Recombinant Poxvirus Vaccination

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e105366 ◽  
Author(s):  
Danushka K. Wijesundara ◽  
Charani Ranasinghe ◽  
Ronald J. Jackson ◽  
Brett A. Lidbury ◽  
Christopher R. Parish ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cross Reactivity ◽  
Functional Avidity ◽  
Cell Responses ◽  
Epitope Variant ◽  
Hiv 1

scholarly journals Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 78 ◽  
Author(s):  
Athina Kilpeläinen ◽  
Narcís Saubi ◽  
Núria Guitart ◽  
Alex Olvera ◽  
Tomáš Hanke ◽  
...  
Keyword(s):  
T Cell ◽  
Miliary Tuberculosis ◽  
T Cell Responses ◽  
T Cell Response ◽  
Expression Vectors ◽  
Effective Vaccine ◽  
Vaccine Platform ◽  
Cell Responses ◽  
Hiv 1 ◽  
Recombinant Bcg

Despite the availability of anti-retroviral therapy, HIV-1 infection remains a massive burden on healthcare systems. Bacillus Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis, confers protection against meningitis and miliary tuberculosis in infants. Recombinant BCG has been used as a vaccine vehicle to express both HIV-1 and Simian Immunodeficiemcy Virus (SIV) immunogens. In this study, we constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HTI.int, expressing the HIVACAT T-cell immunogen (HTI). The plasmid was transformed into a lysine auxotrophic Mycobacterium bovis BCG strain (BCGΔLys) to generate the vaccine BCG.HTI2auxo.int. The DNA sequence coding for the HTI immunogen and HTI protein expression were confirmed, and working vaccine stocks were genetically and phenotypically characterized. We demonstrated that the vaccine was stable in vitro for 35 bacterial generations, and that when delivered in combination with chimpanzee adenovirus (ChAd)Ox1.HTI in adult BALB/c mice, it was well tolerated and induced HIV-1-specific T-cell responses. Specifically, priming with BCG.HTI2auxo.int doubled the magnitude of the T-cell response in comparison with ChAdOx1.HTI alone while maintaining its breadth. The use of integrative expression vectors and novel HIV-1 immunogens can aid in improving mycobacterial vaccine stability as well as specific immunogenicity. This vaccine candidate may be a useful tool in the development of an effective vaccine platform for priming protective responses against HIV-1/TB and other prevalent pediatric pathogens.

scholarly journals Broad and Cross-Clade CD4+ T-Cell Responses Elicited by a DNA Vaccine Encoding Highly Conserved and Promiscuous HIV-1 M-Group Consensus Peptides

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e45267 ◽  
Author(s):  
Rafael Ribeiro Almeida ◽  
Daniela Santoro Rosa ◽  
Susan Pereira Ribeiro ◽  
Vinicius Canato Santana ◽  
Esper Georges Kallás ◽  
...  
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Group Consensus ◽  
Cell Responses ◽  
Hiv 1

scholarly journals Vaccination with a Shigella DNA Vaccine Vector Induces Antigen-Specific CD8+ T Cells and Antiviral Protective Immunity

2001 ◽  
Vol 75 (20) ◽  
pp. 9665-9670 ◽  
Author(s):  
Mohamed T. Shata ◽  
David M. Hone
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
Protective Immunity ◽  
Dna Vaccines ◽  
T Cell Responses ◽  
T Cell Response ◽  
Vaccine Vector ◽  
Host Cells ◽  
Cell Responses ◽  
Hiv 1

ABSTRACT A prototype Shigella human immunodeficiency virus type 1 (HIV-1) gp120 DNA vaccine vector was constructed and evaluated for immunogenicity in a murine model. For comparative purposes, mice were also vaccinated with a vaccinia virus-env(vaccinia-env) vector or the gp120 DNA vaccine alone. Enumeration of the CD8+-T-cell responses to gp120 after vaccination using a gamma interferon enzyme-linked spot assay revealed that a single intranasal dose of the Shigella HIV-1 gp120 DNA vaccine vector elicited a CD8+ T-cell response to gp120, the magnitude of which was comparable to the sizes of the analogous responses to gp120 that developed in mice vaccinated intraperitoneally with the vaccinia-env vector or intramuscularly with the gp120 DNA vaccine. In addition, a single dose of the Shigella gp120 DNA vaccine vector afforded significant protection against a vaccinia-env challenge. Moreover, the number of vaccinia-env PFU recovered in mice vaccinated intranasally with the Shigella vector was about fivefold less than the number recovered from mice vaccinated intramuscularly with the gp120 DNA vaccine. Since theShigella vector did not express detectable levels of gp120, this report confirms that Shigella vectors are capable of delivering passenger DNA vaccines to host cells and inducing robust CD8+ T-cell responses to antigens expressed by the DNA vaccines. Furthermore, to our knowledge, this is the first documentation of antiviral protective immunity following vaccination with a live Shigella DNA vaccine vector.

scholarly journals The GM-CSF–IRF5 signaling axis in eosinophils promotes antitumor immunity through activation of type 1 T cell responses

2020 ◽  
Vol 217 (12) ◽  
Author(s):  
Isabelle C. Arnold ◽  
Mariela Artola-Boran ◽  
Alessandra Gurtner ◽  
Katrin Bertram ◽  
Michael Bauer ◽  
...  
Keyword(s):  
T Cell ◽  
Antitumor Immunity ◽  
Critical Role ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Tumor Control ◽  
Gm Csf ◽  
Cell Responses

The depletion of eosinophils represents an efficient strategy to alleviate allergic asthma, but the consequences of prolonged eosinophil deficiency for human health remain poorly understood. We show here that the ablation of eosinophils severely compromises antitumor immunity in syngeneic and genetic models of colorectal cancer (CRC), which can be attributed to defective Th1 and CD8+ T cell responses. The specific loss of GM-CSF signaling or IRF5 expression in the eosinophil compartment phenocopies the loss of the entire lineage. GM-CSF activates IRF5 in vitro and in vivo and can be administered recombinantly to improve tumor immunity. IL-10 counterregulates IRF5 activation by GM-CSF. CRC patients whose tumors are infiltrated by large numbers of eosinophils also exhibit robust CD8 T cell infiltrates and have a better prognosis than patients with eosinophillow tumors. The combined results demonstrate a critical role of eosinophils in tumor control in CRC and introduce the GM-CSF–IRF5 axis as a critical driver of the antitumor activities of this versatile cell type.

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