Introduction Bentonite, the commercial name for montmorillonite, is the active mineral derived fr... more Introduction Bentonite, the commercial name for montmorillonite, is the active mineral derived from weathered volcanic ash. It has the unusual properties of a sheet-type or platelet structure with extremely large surface area and an inherent negative charge on the platelet. Although their dimensions in the length and width directions can be measured in the hundreds of nanometers, the mineral's thickness is only one nanometer. As a result, individual sheets have aspect ratios (L/W) varying from 200 to 1000 with a majority of platelets in the 200-400 range after purification and nano modification. One especially interesting feature of the bentonite clay is the surface of the platelet can be chemically modified to enhance the clay's ability to absorb and bind toxins, poisons, and viruses. Thus one can modify the bentonite clay surface with one or more metallic cations, organic cations, and combinations designed to maximise the interaction with the viruses. The use of bentonite ...
Background: Developing strategies for controlling the severity of pandemic influenza is a global ... more Background: Developing strategies for controlling the severity of pandemic influenza is a global public health priority. In the event of a pandemic there may be a place for inexpensive, readily available, effective adjunctive therapies to support containment strategies such as prescription antivirals, vaccines, quarantine and restrictions on travel. Inactivation of virus in the intranasal environment is one possible approach. The work described here investigated the sensitivity of influenza viruses to low pH, and the activity of low pH nasal sprays on the course of an influenza infection in the ferret model.
Protective immunity against influenza virus infection is mediated by neutralizing antibodies, but... more Protective immunity against influenza virus infection is mediated by neutralizing antibodies, but the precise role of T cells in human influenza immunity is uncertain. We conducted influenza infection studies in healthy volunteers with no detectable antibodies to the challenge viruses H3N2 or H1N1. We mapped T cell responses to influenza before and during infection. We found a large increase in
We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5... more We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/ Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and morbidity arising from infection with HPAI H5N1 virus.
printing supported by Chiesi Farmaceutici SpA. Visit Chiesi Farmaceutici SpA. at Stand B.40 E-Com... more printing supported by Chiesi Farmaceutici SpA. Visit Chiesi Farmaceutici SpA. at Stand B.40 E-Communication Session Room C9c -10:45-12:45
FluINsure is an intranasal influenza vaccine containing inactivated antigens with the Proteosome... more FluINsure is an intranasal influenza vaccine containing inactivated antigens with the Proteosome adjuvant. Preclinical and human data have shown a good safety profile and immune responses in both the systemic compartment and mucosal compartments. We immunized ...
We have investigated whether 'at risk' subjects who did not respond serologically during a pre-st... more We have investigated whether 'at risk' subjects who did not respond serologically during a pre-study vaccination with a commercial egg grown influenza sub-unit vaccine would respond to a subsequent vaccination with either a single dose of MDCK cell grown influenza vaccine or a standard egg grown influenza vaccine containing the same virus strains. We studied 48 non-responder subjects with a mean age 67.5, range: 34-82 years. In this non-responder group the increased immune response that was detected after boosting with an MDCK cell derived vaccine response was variable and relatively modest, except for the A/Texas strain in the vaccine. The proportion of subjects, with an HI titre of ≥40 (protective antibody titre) increased from 50 to 83% (A/Texas strain), from 13 to 25% (B/Harbin strain) and from 38 to 46% (A/Wuhan strain). In comparison a booster vaccination with egg-derived influenza vaccine resulted in an increase immune response with an HI antibody titre ≥40 for two of the three strains, namely from 17 to 58% for the B/Harbin strain and from 8 to 33% for the A/Wuhan strain.
HLA alleles and hemagglutination-inhibition response to influenza subunit vaccination in unrelate... more HLA alleles and hemagglutination-inhibition response to influenza subunit vaccination in unrelated at-risk donors. ... . Human influenza. In: Nicholson KG, Webster RG, editors. Textbook of influenza. Oxford, UK: Blackwell Science; 1998. p. 216-64. ... . Advances in influenza ...
We applied this technology to the development of a pandemic H5N1 vaccine candidate. The vaccine v... more We applied this technology to the development of a pandemic H5N1 vaccine candidate. The vaccine virus was constructed by reverse genetics in Vero cells, as a 5∶3 reassortant, encoding four proteins HA, NA, M1, and M2 of the A/Vietnam/1203/04 virus while the remaining ...
We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common hous... more We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission.
Introduction Bentonite, the commercial name for montmorillonite, is the active mineral derived fr... more Introduction Bentonite, the commercial name for montmorillonite, is the active mineral derived from weathered volcanic ash. It has the unusual properties of a sheet-type or platelet structure with extremely large surface area and an inherent negative charge on the platelet. Although their dimensions in the length and width directions can be measured in the hundreds of nanometers, the mineral's thickness is only one nanometer. As a result, individual sheets have aspect ratios (L/W) varying from 200 to 1000 with a majority of platelets in the 200-400 range after purification and nano modification. One especially interesting feature of the bentonite clay is the surface of the platelet can be chemically modified to enhance the clay's ability to absorb and bind toxins, poisons, and viruses. Thus one can modify the bentonite clay surface with one or more metallic cations, organic cations, and combinations designed to maximise the interaction with the viruses. The use of bentonite ...
Background: Developing strategies for controlling the severity of pandemic influenza is a global ... more Background: Developing strategies for controlling the severity of pandemic influenza is a global public health priority. In the event of a pandemic there may be a place for inexpensive, readily available, effective adjunctive therapies to support containment strategies such as prescription antivirals, vaccines, quarantine and restrictions on travel. Inactivation of virus in the intranasal environment is one possible approach. The work described here investigated the sensitivity of influenza viruses to low pH, and the activity of low pH nasal sprays on the course of an influenza infection in the ferret model.
Protective immunity against influenza virus infection is mediated by neutralizing antibodies, but... more Protective immunity against influenza virus infection is mediated by neutralizing antibodies, but the precise role of T cells in human influenza immunity is uncertain. We conducted influenza infection studies in healthy volunteers with no detectable antibodies to the challenge viruses H3N2 or H1N1. We mapped T cell responses to influenza before and during infection. We found a large increase in
We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5... more We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/ Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and morbidity arising from infection with HPAI H5N1 virus.
printing supported by Chiesi Farmaceutici SpA. Visit Chiesi Farmaceutici SpA. at Stand B.40 E-Com... more printing supported by Chiesi Farmaceutici SpA. Visit Chiesi Farmaceutici SpA. at Stand B.40 E-Communication Session Room C9c -10:45-12:45
FluINsure is an intranasal influenza vaccine containing inactivated antigens with the Proteosome... more FluINsure is an intranasal influenza vaccine containing inactivated antigens with the Proteosome adjuvant. Preclinical and human data have shown a good safety profile and immune responses in both the systemic compartment and mucosal compartments. We immunized ...
We have investigated whether 'at risk' subjects who did not respond serologically during a pre-st... more We have investigated whether 'at risk' subjects who did not respond serologically during a pre-study vaccination with a commercial egg grown influenza sub-unit vaccine would respond to a subsequent vaccination with either a single dose of MDCK cell grown influenza vaccine or a standard egg grown influenza vaccine containing the same virus strains. We studied 48 non-responder subjects with a mean age 67.5, range: 34-82 years. In this non-responder group the increased immune response that was detected after boosting with an MDCK cell derived vaccine response was variable and relatively modest, except for the A/Texas strain in the vaccine. The proportion of subjects, with an HI titre of ≥40 (protective antibody titre) increased from 50 to 83% (A/Texas strain), from 13 to 25% (B/Harbin strain) and from 38 to 46% (A/Wuhan strain). In comparison a booster vaccination with egg-derived influenza vaccine resulted in an increase immune response with an HI antibody titre ≥40 for two of the three strains, namely from 17 to 58% for the B/Harbin strain and from 8 to 33% for the A/Wuhan strain.
HLA alleles and hemagglutination-inhibition response to influenza subunit vaccination in unrelate... more HLA alleles and hemagglutination-inhibition response to influenza subunit vaccination in unrelated at-risk donors. ... . Human influenza. In: Nicholson KG, Webster RG, editors. Textbook of influenza. Oxford, UK: Blackwell Science; 1998. p. 216-64. ... . Advances in influenza ...
We applied this technology to the development of a pandemic H5N1 vaccine candidate. The vaccine v... more We applied this technology to the development of a pandemic H5N1 vaccine candidate. The vaccine virus was constructed by reverse genetics in Vero cells, as a 5∶3 reassortant, encoding four proteins HA, NA, M1, and M2 of the A/Vietnam/1203/04 virus while the remaining ...
We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common hous... more We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission.
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