Author: Babb, Rachelle ; Paton, James C. ; Kara, Ervin E. ; Ogunniyi, Abiodun D. ; Alsharifi, Mohammed ; McColl, Shaun R. ; Hirst, Timothy R. ; Chen, Austen

Streptococcus pneumoniae and influenza are the world's foremost bacterial and viral respiratory pathogens. We have previously described a γ-irradiated influenza A virus (γ-FLU) vaccine that provides cross-protective immunity against heterosubtypic infections. More recently, we reported a novel non-adjuvanted γ-irradiated S. pneumoniae (γ-PN) vaccine that elicits serotype-independent protection. Considering the clinical synergism of both pathogens, combination of a serotype-independent pneumococcal vaccine with a broad-spectrum influenza vaccine to protect against both infections would have a considerable clinical impact. In the present study, we co-immunized C57BL/6 mice intranasally (IN) with a mixture of γ-PN (whole inactivated cells) and γ-FLU (whole inactivated virions) and examined protective efficacy. Co-immunization enhanced γ-PN vaccine efficacy against virulent pneumococcal challenge, which was dependent on CD4+ T-cell responses. In contrast, vaccination with γ-PN alone, co-immunization enhanced pneumococcal-specific effector T-helper 17 cell (Th17) and Th1 memory cell, promoted development of CD4+ tissue-resident memory (TRM) cells and enhanced Pneumococcus-specific antibody responses. Furthermore, co-immunization elicited significant protection against lethal influenza challenge, as well as against co-infection with both influenza and S. pneumoniae. This is the first report showing the synergistic effect of combining whole cell and whole virion vaccines to both S. pneumoniae and influenza as a single vaccine to protect against individual and co-infection, without compromising pathogen-specific immunity.

01 Jul 2014·Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology

[Effect of L-ornithine L-aspartate granules in treating chronic liver disease in patients with high-level serum gamma-glutamyltransferase].

Article

Author: Yan Z ; Wang Y ; Wang J ; Zhang X ; Xiang Dd ; Wang X ; Jiang L ; Mao Q ; Jiang Y

OBJECTIVETo explore the clinical effect of L-ornithine L-aspartate (LOLA) granules in treating chronic liver disease in patients with high-level serum gamma-glutamyltransferase (G-GT) using a 24-week treatment course.METHODSTwo-hundred patients with chronic liver disease and above normal G-GT were given a 12-week course of LOLA granules (9 g/d) and then classified into the following three groups according to the change in serum Gamma-GT:group I:patients with Gamma-GT level returned to normal;group II:patients with serum Gamma-GT level that was reduced during the treatment; group III:patients with serum Gamma-GT level that did not decrease or that increased to a higher level than at start of treatment.After the 12-week treatment course, the patients in group I were divided into three subgroups for receipt of a control drug (compound glycyrrhizin, 50mg/d) or an additional 12-week course of Gamma-GT at a reduced dose (LOLA granules 3 g/d) or at the original dose; groups II and III were maintained on the initial dose for an additional 12 weeks.The groups were reassessed at the end of the second 12-week course (at the end of week 24 of the study's observation period).Count data were compared using the x2 test and measurement data were compared using the t-test.RESULTSIn group I, the serum Gamma-GT level was 90.9% at the end of the first 12-week course and dropped to a mean level of 52.2% for both of the subgroups that received the reduced and original dose after the additional 12 weeks of LOLA granules treatment; the difference from week 12 to week 24 was significant (x2=8.213, P less than 0.05).The 24-week change in serum Gamma-GT levels for the group I reduced and original dose subgroups vs.the control subgroup were also significantly different from those seen in groups II and III (P less than 0.05).The percentage of patients in group I who achieved normal level serum Gamma-GT after 24 weeks of treatment (78.6%) was significantly higher than that for the control group (vs.55.0%, x2=11.452, P less than 0.05).When the patients in group 1 who had received the 12 additional weeks of LOLA granules treatment were measured again at two weeks after the treatments had been discontinued (end of week 26), the percentage of patients with normal serum Gamma-GT level was 92.7%, with only three cases showing obviously abnormal levels; in contrast, the group I patients in the control group of the second 12-week study period had on 66.7% of patients with normal-level serum Gamma-GT.The difference in change between the treated groups (both reduced and original dose) and the control group was significant (x2=14.964, P less than 0.05).CONCLUSIONPatients whose serumGamma-GT levels returned to normal after receipt of LOLA granules for 12 weeks benefitted from an additional 12 weeks of consolidation treatment, and those given the treatment at the original dose benefitted most.Compared with the compound glycyrrhizin, LOLA granules provided a better maintenance of resolved Gamma-GT level.Therefore, the effect of LOLA appears to be reliable and stable as well as safe for clinical use.

01 Jun 2010·AtherosclerosisQ2 · MEDICINE

Gamma-glutamyltransferase and prognosis in patients with stable coronary heart disease followed over 8 years

Q2 · MEDICINE

Article

Author: H. Hahmann ; L.P. Breitling ; B. Wüsten ; H. Brenner ; D. Rothenbacher ; N.C. Grandi

OBJECTIVESSerum gamma-glutamyltransferase (gamma-GT) predicts incident cardiovascular disease and mortality. The present study examined whether gamma-GT also is associated with prognosis in patients with stable coronary heart disease.METHODS AND RESULTSThis study included 1152 participants (aged 30-70 years at baseline) of an in-patient rehabilitation programme after acute coronary syndrome, recruited in two rehabilitation clinics in Germany in the years 1999-2000 (KAROLA study). Until year 8 follow-up, 147 participants had experienced a non-fatal or fatal secondary cardiovascular disease event. Confounder-adjusted Cox proportional hazards models revealed an increase in risk for secondary events over ascending gamma-GT quartiles, with hazard ratios (95% confidence interval) of 1.21 (0.72-2.03), 1.32 (0.80-2.16) and 1.75 (1.08-2.83) for the 2nd, 3rd and 4th in reference to the lowest quartile (Ptrend=0.024). The association with all-cause mortality examined as a secondary outcome was slightly stronger (hazard ratio of 4th quartile: 1.97 [1.15-3.36]; Ptrend=0.017).CONCLUSIONSIn patients with stable coronary heart disease, serum gamma-GT was associated with prognosis independent of a variety of established risk markers. The association appeared similar to that reported for primary cardiovascular disease, which should motivate additional studies of its clinical utility in cardiovascular patient care.

News (Medical) associated with Gamma-PN

03 Jan 2024

·www.prnewswire.com

GPN Vaccines Reports Positive Safety and Immunogenicity Data from its Phase 1 Trial of Gamma-PN

ADELAIDE, Australia, Jan. 3, 2024 /PRNewswire/ -- GPN Vaccines Ltd, a clinical-stage biotechnology company developing a Streptococcus pneumoniae vaccine to prevent life-threatening pneumonia, bacteraemia and meningitis, is pleased to announce positive safety and immunogenicity data from its Phase 1 trial of Gamma-PN, a non-adjuvanted whole cell-pneumococcal vaccine being investigated in adults aged 50 to 69 years. In this double-blind, randomised study with placebo and active controls, 120 participants received either two doses of 50, 250 or 1000 micrograms of Gamma-PN (n=30 per group); a single dose of licensed pneumococcal vaccine (Pneumovax-23® or Prevenar 13®, n=9 per group); or placebo. The study met its primary safety objective, demonstrating a safety profile suitable for further development. There were no serious adverse events following administration of Gamma-PN and systemic tolerability was considered excellent. Injection site reactions were largely confined to mild to moderate erythema and swelling, typically of short (1-2 day) duration, with the frequency and extent being dose-related. Local and systemic tolerability after the second injection of Gamma-PN was similar to that after the first. An immunological assessment of serum IgG responses to vaccination with Gamma-PN was performed using an ELISA developed and run by a GLP-accredited third-party laboratory. This demonstrated that Gamma-PN induced dose-dependent rises in serum IgG levels to Gamma-PN after both the first and second vaccine dose. Neutrophil activation in participants administered Gamma-PN was consistent with vaccine stimulation of innate immune responses. GPN Vaccines is also conducting additional immunological tests on serum and peripheral blood mononuclear cells (PBMCs), including an assessment of opsonophagocytic antibodies against Streptococcus pneumoniae serotypes covered by current licensed pneumococcal vaccines as well as serotypes not covered by such vaccines. These results will be reported once complete. Professor Paul Rolan, GPN Vaccines' Chief Medical Officer commented "I would like to extend my appreciation to all of the participants who volunteered to be in this clinical trial. The study demonstrated that Gamma-PN is safe, well tolerated and encompassed the doses to be selected for further clinical development. " Dr Tim Hirst, Chief Executive Officer and co-founder said "I am delighted we can announce positive clinical trial results on our broad-spectrum pneumococcal vaccine designed to offer protection against all serotypes of Streptococcus pneumoniae. These results provide important insights that will support dose selection for future Phase 2 clinical trials". This trial was generously supported by a $1 million grant from the South Australian Government's Research and Innovation Fund (RIF). About GPN Vaccines GPN Vaccines is a public (unlisted) biotechnology company developing a vaccine against Streptococcus pneumoniae, which is responsible for causing life-threatening pneumonia, bacteraemia and meningitis, as well as otitis media (middle ear infections). Each year it causes 1-2 million deaths worldwide, killing more children than AIDS, malaria and tuberculosis combined. There are now more than 100 different serotypes of S. pneumoniae and the best vaccine currently on the market only protects against 20 of them. GPN Vaccines' product, called Gamma-PN, is being developed to protect children and adults against all S. pneumoniae strains, regardless of serotype. SOURCE GPN Vaccines

VaccineClinical ResultPhase 1

06 Nov 2023

·www.prnewswire.com

BioCina Expands Partnership with GPN Vaccines

ADELAIDE, South Australia, Nov. 6, 2023 /PRNewswire/ -- BioCina Pty Ltd., a global end-to-end biologics contract development and manufacturing organization (CDMO), announced the expansion of their partnership with GPN Vaccines Ltd. GPN Vaccines is a biotechnology company developing a proprietary engineered whole-cell vaccine called Gamma-PN™ against Streptococcus pneumoniae. This bacterium is responsible for causing life-threatening infections such as pneumonia, bacteraemia and meningitis, each year causing up to 2 million deaths worldwide. GPN's vaccine technology is a proprietary engineered strain of Streptococcus pneumoniae that lacks capsular polysaccharide and expresses surface proteins common to all serotypes, inducing broad-spectrum T- and B-cell immunity to cross-reactive protein antigens of the bacteria, making this vaccine outperform against currently approved vaccines. Continue Reading "We are extremely proud that GPN Vaccines has asked BioCina to further scale-up the production of Gamma-PN." Post this BioCina, global CDMO, announced the expansion of their partnership with GPN Vaccines Ltd. BioCina has a rich history of developing and manufacturing recombinant proteins in microbial systems such as E. coli. BioCina will manufacture large-scale cGMP batches for this program. The BioCina facility in Adelaide, Australia has a rich history of developing and manufacturing recombinant proteins in microbial systems such as E. coli. BioCina's Chief Executive Officer, Mark W. Womack stated, "We are extremely proud that GPN Vaccines has asked us to further scale-up the production of Gamma-PN™, which has the potential to protect so many lives against a broad range of serotypes not covered by any current vaccines." GPN Vaccines' Chairman & Chief Executive Officer, Professor Tim Hirst said, "We are delighted to be progressing with the next stage of cGMP manufacture of our innovative whole cell pneumococcal vaccine, Gamma-PN™, with BioCina as the CDMO of choice. They successfully optimised the manufacture of Phase 1 material, and we now look forward to working with them to deliver a scaled-up process for the manufacture of Phase 2 material suitable for clinical evaluation worldwide." About BioCina BioCina is a global end-to-end biologics contract development and manufacturing organization (CDMO) of choice, offering process development and cGMP clinical & commercial manufacturing of the microbial, plasmid DNA and mRNA modalities. Our US FDA, EMA and TGA approved site in South Australia, is staffed with a tremendously experienced technical and operations team, with most critical SME's having an average tenure of 15+ years at the Adelaide site. BioCina delivers high-quality, cost-effective CDMO services, including cell line development, process development, and cGMP drug substance manufacturing solutions across the modalities we serve. To address the ever-evolving requirements of our current and future clients, we are adding a 2000L microbial fermenter and large-scale mRNA manufacturing in our Adelaide facility, and we will be establishing a second facility with Mammalian PD and large-scale manufacturing. To learn more visit . About GPN Vaccines GPN Vaccines is a public (unlisted) biotechnology company developing a vaccine against Streptococcus pneumoniae, which is responsible for causing life-threatening pneumonia, bacteremia, and meningitis, as well as otitis media (middle ear infections). Each year it causes 1-2 million deaths worldwide, killing more children than AIDS, malaria and tuberculosis combined. There are now more than 100 different serotypes of S. pneumoniae and the best vaccine currently on the market only protects against 20 of them. GPN Vaccines' product, called Gamma-PN™, is being developed to protect children and adults against all S. pneumoniae strains, regardless of serotype. To learn more visit BioCina Contact Details BioCina Pty Ltd. 8 Dalgleish St, Thebarton, Adelaide, South Australia 5031 Kamal Preet, VP Business Development and Marketing +61 452 625 977 GPN Vaccine Contact Details Professor Tim Hirst, [email protected], +61 420 942 824 Miriam Dodd, [email protected], +61 411 455 622 Media Contact Chuck Miller [email protected] +1 720-560-5580 SOURCE BioCina

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Indication	Highest Phase	Country/Location	Organization	Date
Pneumococcal Infections	Phase 1	AU	GPN Vaccines Ltd.	16 Jan 2023

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