Jorma Hinkula | Linköping University (original) (raw)

Papers by Jorma Hinkula

PLOS ONE

Potent broad-spectrum antiviral agents are urgently needed to combat existing and emerging viral ... more Potent broad-spectrum antiviral agents are urgently needed to combat existing and emerging viral infections. This is particularly important considering that vaccine development is a costly and time consuming process and that viruses constantly mutate and render the vaccine ineffective. Antimicrobial peptides (AMP), such as bacteriocins, are attractive candidates as antiviral agents against enveloped viruses. One of these bacteriocins is PLNC8 αβ, which consists of amphipathic peptides with positive net charges that display high affinity for negatively charged pathogen membrane structures, including phosphatidylserine rich lipid membranes of viral envelopes. Due to the morphological and physiological differences between viral envelopes and host cell plasma membranes, PLNC8 αβ is thought to have high safety profile by specifically targeting viral envelopes without effecting host cell membranes. In this study, we have tested the antiviral effects of PLNC8 αβ against the flaviviruses La...

ACS Applied Materials & Interfaces

Longitudinal serum samples, nasopharyngeal/nasal swabs and rectal swab samples were collected fro... more Longitudinal serum samples, nasopharyngeal/nasal swabs and rectal swab samples were collected from eighty-nine individuals (median age 66 y) with SARS-CoV-2 PCR-positive test results at Linköping University Hospital. Samples were collected from the initial visit and thereafter for up to 2 years of follow-up. The presence of serum IgG and IgA against SARS-CoV-2 antigens (S1-spike, nucleocapsid, and NSP3) was analysed. Nasal and rectal swabs were tested for the presence of mucosal IgA against the outer envelope S1 spike and the nucleocapsid protein. Ninety percent of the participants were seropositive for SARS-CoV-2 recombinant proteins on Day 28 after study entry, and all (100%) were seropositive based on samples collected 2 months or later. Almost all (95%) developed serum SARS-CoV-2-neutralizing antibodies that were measurable from 6 to 24 months. The most common antibody responses (both serum IgG, mainly IgG1, and in nasal mucosa IgA) reacted with the S1-spike protein and the nucl...

Trends in Biotechnology

Despite the great success of vaccines over two centuries, the conventional strategy is based on a... more Despite the great success of vaccines over two centuries, the conventional strategy is based on attenuated/altered microorganisms. However, this is not effective for all microbes and often fails to elicit a protective immune response, and sometimes poses unexpected safety risks. The expanding nano toolbox may overcome some of the roadblocks in vaccine development given the plethora of unique nanoparticle (NP)-based platforms that can successfully induce specific immune responses leading to exciting and novel solutions. Nanovaccines necessitate a thorough understanding of the immunostimulatory effect of these nanotools. We present a comprehensive description of strategies in which nanotools have been used to elicit an immune response and provide a perspective on how nanotechnology can lead to future personalized nanovaccines.

Clinical and Experimental Immunology, Aug 1, 1992

Human MoAbsof IgM class were developed against three regions of the HIV-1 envelope. Uninfeeted do... more Human MoAbsof IgM class were developed against three regions of the HIV-1 envelope. Uninfeeted donor lymphocytes were immunized in vitro with recombinant protein pBI. Four out of five antibodies were directed to different parts ofthe V3 region, which contains a major neutralizing site. Two out of these antibodies were directed to more than one amino acid sequence, indicating reactivity to discontinuous sites. Two of the human MoAbs inhibited viral spread between cells in tissue culture, interpreted as reactivities to conserved amino acid sequences exposed during viral maturation. No MoAb neutralized virus, which may be explained by the relatively low avidity of the antibodies. One MoAb was directed to a region containing amino acids participating in CD4 binding. This technique appears to allow formation of antibodies with fine specificities other than those obtained in infected hosts.

At this time when vaccine development is at its peak against different respiratory diseases, it i... more At this time when vaccine development is at its peak against different respiratory diseases, it is of utmost importance to find suitable adjuvants that can increase the potency of the vaccine candidates. In this study, we have shown how anionic and cationic lipid adjuvants can differ in their mechanism to induce immune protection against influenza. In presence of Hemagglutinin (HA) antigen, the anionic adjuvant (L3) induces enhanced dendritic cell activity, CD80, and CD86 costimulatory marker expression, MHCII, and DEC205 expression, and T cell activation. On the contrary, the cationic adjuvant (N3) induces MHCI expression on dendritic cells along with the higher Th17 cell population and enhanced CD28 expression and activation of CD8T cells. They exhibited significantly higher interferon-gamma (IFNγ) within both CD4T and CD8T cells. L3 treated groups produce significantly higher B plasma cells and higher titers of anti-HA IgG and IgA with more neutralization capacity of the live vir...

Scandinavian Journal of Rheumatology, 2021

Vaccines

The use of nanoparticles for developing vaccines has become a routine process for researchers and... more The use of nanoparticles for developing vaccines has become a routine process for researchers and pharmaceutical companies. Gold nanoparticles (GNPs) are chemical inert, have low toxicity, and are easy to modify and functionalize, making them an attractive choice for nanovaccine development. GNPs are modified for diagnostics and detection of many pathogens. The biocompatibility and biodistribution properties of GNPs render them ideal for use in clinical settings. They have excellent immune modulatory and adjuvant properties. They have been used as the antigen carrier for the delivery system to a targeted site. Tagging them with antibodies can direct the drug or antigen-carrying GNPs to specific tissues or cells. The physicochemical properties of the GNP, together with its dynamic immune response based on its size, shape, surface charge, and optical properties, make it a suitable candidate for vaccine development. The clear outcome of modulating dendritic cells, T and B lymphocytes, ...

Analytical Cellular Pathology

The oncogenic potential of hepatitis C virus (HCV) core protein has been demonstrated, but the pr... more The oncogenic potential of hepatitis C virus (HCV) core protein has been demonstrated, but the precise mechanism of cell transformation triggered by HCV core is still unclear. This study shows that constitutive expression of HCV core protein (core) in NIH 3T3 murine fibroblasts triggers malignant transformation. At the preneoplastic stage, clones that expressed HCV core constitutively demonstrated genomic instability seen as disruption of the mitotic spindle cell checkpoint leading to increased ploidy. Transformation was completed by the loss of DNA and resistance to apoptosis induced by serum starvation. Simultaneously, cells acquired a capacity for anchorage independent growth and absence of contact inhibition. Inoculation of these transformed cells into severe combined immune deficiency (SCID) mice led to formation of solid core-expressing tumors. Transformation and tumorigenicity of core-expressing cell lines coincided with a 5- to 10-fold repression of endogenous p53 transactiv...

Frontiers in Immunology, 2021

ObjectivesImpact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on ... more ObjectivesImpact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on individuals with arthritis has been highlighted whereas data on other rheumatic diseases, e.g., systemic lupus erythematosus (SLE), are scarce. Similarly to SLE, severe SARS-CoV-2 infection includes risks for thromboembolism, an unbalanced type I interferon response, and complement activation. Herein, SARS-CoV-2 antibodies in longitudinal samples collected prior to vaccination were analyzed and compared with SLE progression and antinuclear antibody (ANA) levels.MethodsOne hundred patients (83 women) with established SLE and a regular visit to the rheumatologist (March 2020 to January 2021) were included. All subjects donated blood and had done likewise prior to the pandemic. SARS-CoV-2 antibody isotypes (IgG, IgA, IgM) to the cell receptor-binding S1-spike outer envelope protein were detected by ELISA, and their neutralizing capacity was investigated. IgG-ANA were measured by multiplex t...

Scientific Reports, 2018

DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized a prototype... more DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized a prototype DNA vaccine against drug-resistant HIV-1 based on a weak Th2-immunogen, HIV-1 reverse transcriptase (RT). We designed expression-optimized genes encoding inactivated wild-type and drug-resistant RTs (RT-DNAs) and introduced them into mice by intradermal injections followed by electroporation. RT-DNAs were administered as single or double primes with or without cyclic-di-GMP, or as a prime followed by boost with RT-DNA mixed with a luciferase-encoding plasmid (“surrogate challenge”). Repeated primes improved cellular responses and broadened epitope specificity. Addition of cyclic-di-GMP induced a transient increase in IFN-γ production. The strongest anti-RT immune response was achieved in a prime-boost protocol with electroporation by short 100V pulses done using penetrating electrodes. The RT-specific response, dominated by CD4+ T-cells, targeted epitopes at aa 199–220 and aa 528–543. D...

AIDS Research and Human Retroviruses, 1991

Five mouse monoclonal antibodies were raised against a recombinant protein comprising the complet... more Five mouse monoclonal antibodies were raised against a recombinant protein comprising the complete sequence of gag24 protein from HTLV-IIIB. All monoclonal antibodies recognized the native protein in enzyme-linked immunosorbant assay (ELISA) and Western blots. All monoclonal antibodies also cross-reacted with an human immunodeficiency virus type 2 (HIV-2) strain in western blots, whereas only one antibody detected HIV-2 p25 in ELISA. By using synthetic peptides, cross-reacting epitopes were mapped and three regions were defined. The conserved immunogenic sites were located in the carboxyterminal region of the protein. Inhibition experiments with human sera showed that this region is also immunogenic in humans.

Clinical and Experimental Immunology, 2000

SUMMARYThe efficacy of DNA-based immunization in conferring protective immunity against certain m... more SUMMARYThe efficacy of DNA-based immunization in conferring protective immunity against certain microbial pathogens including human immunodeficiency virus type 1 (HIV-1) has been described. The potential advantage of DNA-based immunization over the traditional vaccines largely results from its capacity to efficiently induce Th1-biased immune responses against an encoded antigen. We describe how Th1-biased immune responses are induced by DNA-based immunization, using a DNA vaccine construct encoding HIV-1 gp160 cDNA and an eukaryotic expression plasmid carrying murine IFN-γ cDNA. Transfection of an eukaryotic expression plasmid carrying immunostimulatory sequences (ISS) as well as a gene of interest (DNA vaccine) into professional antigen presenting cells (APC) induced transactivation of IL-12 mRNA, which resulted in antigen-specific Th1-biased immune responses against the encoded antigen. Th1-biased immune responses induced by DNA-based immunization were substantially upregulated by...

To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often need... more To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often needed. To date, no mucosal adjuvants are approved for human use, however, there are a variety of mucosa ...

Research Square (Research Square), Mar 1, 2021

Treatment with RNAi against HIV-1 transcripts e ciently inhibits viral replication but induces se... more Treatment with RNAi against HIV-1 transcripts e ciently inhibits viral replication but induces selection of escape mutants; therefore, the CCR5 coreceptor was suggested as an additional target. Blocking viral and host transcripts improved the antiviral effect. We have used short hairpin RNA (shRNA) targeting the human CCR5 (shCCR5) or the HIV-1 rev (shRev) transcripts to demonstrate distinctive properties of anti-CCR5 shRNA: shCCR5 induced more sustained protection than shRev; partial reduction in CCR5 expression substantially decreased HIV-1 infection, and shCCR5 performed better than shRev in the mixed shRNA-treated and untreated cultures. These observations indicate that CCR5 inhibitors should be conveniently included in HIV-1 gene silencing treatment schedules when only a certain cell fraction is protected to further reduce endogenous virus in a properly ART-treated HIV-1 infected individual.

Journal of Medical Virology, Nov 1, 1999

Rotavirus nonstructural protein NSP4 has recently been suggested to function as a viral enterotox... more Rotavirus nonstructural protein NSP4 has recently been suggested to function as a viral enterotoxin and play a role in the pathophysiological mechanism whereby rotaviruses induce diarrhea. The ability of rotavirus NSP4 to stimulate a humoral immune response was examined in ...

bioRxiv (Cold Spring Harbor Laboratory), Mar 18, 2019

Journal of Virology, Aug 1, 1989

Murine monoclonal antibodies directed against the structural proteins p17 and p24 of human immuno... more Murine monoclonal antibodies directed against the structural proteins p17 and p24 of human immunodeficiency virus type 1 were investigated in an epitope mapping system. Overlapping peptides consisting of 15 amino acids of the p17 and p24 protein, respectively, were used as competitors in an enzyme-linked immunosorbent assay. Three different immunogenic regions (A, B, and C) could be defined, one on p17 and two on p24. Twenty monoclonal antibodies reacted with the human immunodeficiency virus type 1 peptides of region B, although differences in the reactivity of these antibodies with human immunodeficiency virus type 2 and simian immunodeficiency virus strain mac were detectable. Recognized epitopes were characterized by computer analysis as described by T.

Research Square (Research Square), Oct 25, 2022

Seasonal in uenza vaccination has different implications on the immune response depending on the ... more Seasonal in uenza vaccination has different implications on the immune response depending on the comorbidities. Diabetes is one such critical disease that increases the patient's susceptibility to in uenza and suppresses vaccine e cacy and immunity. The sex of the individuals also plays a de nitive role in it. This study aims to understand the e cacy of the seasonal vaccine against in uenza in diabetic groups and undergoing immune mechanisms in both sexes. There is a switching of the female with diabetes towards stronger cell-mediated immunity and Th1/Th17 response with suppressed humoral immunity. They show enhanced proin ammatory activities within T cells, CD8T activation, Th17 proliferation, and the majority of IgG2 antibody subtypes with reduced neutralization potential. Males with diabetes exhibit enhanced humoral Th2-immunity than the nondiabetic group. They exhibit higher MHCII, and DEC205 levels in dendritic cells, an increase in plasma B lymphocytes, and in uenza-haemagglutinin speci c IgG titer with stronger virus neutralization potential. This study highlights the critical immune mechanisms and sex-speci c swapping of their preferred immune response pathways against in uenza after vaccination during diabetes. We propose a need for a sex-speci c customized vaccine regimen to be implemented against in uenza for individuals having diabetes to exploit the manifested strength and weakness in their protective immunity.