Limits...
Prevention and treatment of influenza with hyperimmune bovine colostrum antibody.

Ng WC, Wong V, Muller B, Rawlin G, Brown LE - PLoS ONE (2010)

Bottom Line: Passive transfer of specific antibody (Ab) may provide a useful means of preventing or treating disease in unvaccinated individuals or those failing to adequately seroconvert, especially now that resistance to antiviral drugs is on the rise.In this study, bovine colostrum, which contains approximately 500 g of IgG per milking per animal, has been investigated as a source of polyclonal antibody for delivery to the respiratory tract.Successful reduction of established infection with this highly virulent virus was also observed with a single treatment 24 hr after virus exposure.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.

ABSTRACT

Background: Despite the availability of specific vaccines and antiviral drugs, influenza continues to impose a heavy toll on human health worldwide. Passive transfer of specific antibody (Ab) may provide a useful means of preventing or treating disease in unvaccinated individuals or those failing to adequately seroconvert, especially now that resistance to antiviral drugs is on the rise. However, preparation of appropriate Ab in large scale, quickly and on a yearly basis is viewed as a significant logistical hurdle for this approach to control seasonal influenza.

Methodology/principal findings: In this study, bovine colostrum, which contains approximately 500 g of IgG per milking per animal, has been investigated as a source of polyclonal antibody for delivery to the respiratory tract. IgG and F(ab')2 were purified from the hyperimmune colostrum of cows vaccinated with influenza A/Puerto Rico/8/34 (PR8) vaccine and were shown to have high hemagglutination-inhibitory and virus-neutralizing titers. In BALB/c mice, a single administration of either IgG or F(ab')2 could prevent the establishment of infection with a sublethal dose of PR8 virus when given as early as 7 days prior to exposure to virus. Pre-treated mice also survived an otherwise lethal dose of virus, the IgG- but not the F(ab')2-treated mice showing no weight loss. Successful reduction of established infection with this highly virulent virus was also observed with a single treatment 24 hr after virus exposure.

Conclusions/significance: These data suggest that a novel and commercially-scalable technique for preparing Ab from hyperimmune bovine colostrum could allow production of a valuable substitute for antiviral drugs to control influenza with the advantage of eliminating the need for daily administration.

Show MeSH

Related in: MedlinePlus

Virus loads are reduced in the lungs after treatment with the anti-PR8 IgG and F(ab')2 preparations.BALB/c mice (n = 4) were infected with 50 pfu of PR8 virus in 50 µl via the TRT route under penthrane anaesthesia. Twenty four hours post-infection, mice were treated with 1000 µg, 800 µg, 500 µg, 200 µg or 100 µg of (A) anti-PR8 IgG or non-immune IgG or (B) anti-PR8 F(ab')2 or non-immune F(ab')2 or PBS via TRT route. Five days post-infection, mice were killed and lungs were collected in 1 ml media. (C) Mice were infected and treated as in (B) and lungs sampled 7 days post infection. Viral titres were determined by plaque assay on MDCK cell monolayers. The experiment was carried out in its entirety once and results are consistent with repeat experiments on selected doses. Each symbol represents an individual mouse and the line represents the mean of each group. Brackets with an asterisk indicate a statistically significant difference (p<0.001) between the indicated groups.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2964324&req=5

pone-0013622-g004: Virus loads are reduced in the lungs after treatment with the anti-PR8 IgG and F(ab')2 preparations.BALB/c mice (n = 4) were infected with 50 pfu of PR8 virus in 50 µl via the TRT route under penthrane anaesthesia. Twenty four hours post-infection, mice were treated with 1000 µg, 800 µg, 500 µg, 200 µg or 100 µg of (A) anti-PR8 IgG or non-immune IgG or (B) anti-PR8 F(ab')2 or non-immune F(ab')2 or PBS via TRT route. Five days post-infection, mice were killed and lungs were collected in 1 ml media. (C) Mice were infected and treated as in (B) and lungs sampled 7 days post infection. Viral titres were determined by plaque assay on MDCK cell monolayers. The experiment was carried out in its entirety once and results are consistent with repeat experiments on selected doses. Each symbol represents an individual mouse and the line represents the mean of each group. Brackets with an asterisk indicate a statistically significant difference (p<0.001) between the indicated groups.

Mentions: We took a similar approach to investigating the ability of different concentrations of Ab to clear virus from the lungs of infected mice after TRT delivery. As with the URT model, the non-immune IgG and F(ab')2 preparations delivered by the TRT route 24 hrs after virus infection provided no reduction of viral loads in the lungs (Fig. 4A and B). However, 100% of mice treated with 1 mg of anti-PR8 IgG had undetectable viral titers in the lungs 5 days later (Fig. 4A). Half of the mice treated with 500 µg and 800 µg of anti-PR8 IgG completely cleared lung virus and the remainder showed partial clearance, with the mean viral titers of these groups significantly lower than the PBS control mice (p<0.001 for both). When mice were treated with lower concentrations of immune IgG (100 µg and 200 µg), no significant decreases in lung viral titres were observed. Treatment with equivalent amounts of anti-PR8 F(ab')2 did not provide complete clearance at any of the doses tested (Fig. 4B). Nevertheless, significant partial clearance was observed, particularly at the highest dose where 100-fold less virus was present in the lungs on day 5 (p<0.001), and also at 800, 500 and 200 µg doses (p<0.05 for all three).


Prevention and treatment of influenza with hyperimmune bovine colostrum antibody.

Ng WC, Wong V, Muller B, Rawlin G, Brown LE - PLoS ONE (2010)

Virus loads are reduced in the lungs after treatment with the anti-PR8 IgG and F(ab')2 preparations.BALB/c mice (n = 4) were infected with 50 pfu of PR8 virus in 50 µl via the TRT route under penthrane anaesthesia. Twenty four hours post-infection, mice were treated with 1000 µg, 800 µg, 500 µg, 200 µg or 100 µg of (A) anti-PR8 IgG or non-immune IgG or (B) anti-PR8 F(ab')2 or non-immune F(ab')2 or PBS via TRT route. Five days post-infection, mice were killed and lungs were collected in 1 ml media. (C) Mice were infected and treated as in (B) and lungs sampled 7 days post infection. Viral titres were determined by plaque assay on MDCK cell monolayers. The experiment was carried out in its entirety once and results are consistent with repeat experiments on selected doses. Each symbol represents an individual mouse and the line represents the mean of each group. Brackets with an asterisk indicate a statistically significant difference (p<0.001) between the indicated groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2964324&req=5

pone-0013622-g004: Virus loads are reduced in the lungs after treatment with the anti-PR8 IgG and F(ab')2 preparations.BALB/c mice (n = 4) were infected with 50 pfu of PR8 virus in 50 µl via the TRT route under penthrane anaesthesia. Twenty four hours post-infection, mice were treated with 1000 µg, 800 µg, 500 µg, 200 µg or 100 µg of (A) anti-PR8 IgG or non-immune IgG or (B) anti-PR8 F(ab')2 or non-immune F(ab')2 or PBS via TRT route. Five days post-infection, mice were killed and lungs were collected in 1 ml media. (C) Mice were infected and treated as in (B) and lungs sampled 7 days post infection. Viral titres were determined by plaque assay on MDCK cell monolayers. The experiment was carried out in its entirety once and results are consistent with repeat experiments on selected doses. Each symbol represents an individual mouse and the line represents the mean of each group. Brackets with an asterisk indicate a statistically significant difference (p<0.001) between the indicated groups.
Mentions: We took a similar approach to investigating the ability of different concentrations of Ab to clear virus from the lungs of infected mice after TRT delivery. As with the URT model, the non-immune IgG and F(ab')2 preparations delivered by the TRT route 24 hrs after virus infection provided no reduction of viral loads in the lungs (Fig. 4A and B). However, 100% of mice treated with 1 mg of anti-PR8 IgG had undetectable viral titers in the lungs 5 days later (Fig. 4A). Half of the mice treated with 500 µg and 800 µg of anti-PR8 IgG completely cleared lung virus and the remainder showed partial clearance, with the mean viral titers of these groups significantly lower than the PBS control mice (p<0.001 for both). When mice were treated with lower concentrations of immune IgG (100 µg and 200 µg), no significant decreases in lung viral titres were observed. Treatment with equivalent amounts of anti-PR8 F(ab')2 did not provide complete clearance at any of the doses tested (Fig. 4B). Nevertheless, significant partial clearance was observed, particularly at the highest dose where 100-fold less virus was present in the lungs on day 5 (p<0.001), and also at 800, 500 and 200 µg doses (p<0.05 for all three).

Bottom Line: Passive transfer of specific antibody (Ab) may provide a useful means of preventing or treating disease in unvaccinated individuals or those failing to adequately seroconvert, especially now that resistance to antiviral drugs is on the rise.In this study, bovine colostrum, which contains approximately 500 g of IgG per milking per animal, has been investigated as a source of polyclonal antibody for delivery to the respiratory tract.Successful reduction of established infection with this highly virulent virus was also observed with a single treatment 24 hr after virus exposure.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.

ABSTRACT

Background: Despite the availability of specific vaccines and antiviral drugs, influenza continues to impose a heavy toll on human health worldwide. Passive transfer of specific antibody (Ab) may provide a useful means of preventing or treating disease in unvaccinated individuals or those failing to adequately seroconvert, especially now that resistance to antiviral drugs is on the rise. However, preparation of appropriate Ab in large scale, quickly and on a yearly basis is viewed as a significant logistical hurdle for this approach to control seasonal influenza.

Methodology/principal findings: In this study, bovine colostrum, which contains approximately 500 g of IgG per milking per animal, has been investigated as a source of polyclonal antibody for delivery to the respiratory tract. IgG and F(ab')2 were purified from the hyperimmune colostrum of cows vaccinated with influenza A/Puerto Rico/8/34 (PR8) vaccine and were shown to have high hemagglutination-inhibitory and virus-neutralizing titers. In BALB/c mice, a single administration of either IgG or F(ab')2 could prevent the establishment of infection with a sublethal dose of PR8 virus when given as early as 7 days prior to exposure to virus. Pre-treated mice also survived an otherwise lethal dose of virus, the IgG- but not the F(ab')2-treated mice showing no weight loss. Successful reduction of established infection with this highly virulent virus was also observed with a single treatment 24 hr after virus exposure.

Conclusions/significance: These data suggest that a novel and commercially-scalable technique for preparing Ab from hyperimmune bovine colostrum could allow production of a valuable substitute for antiviral drugs to control influenza with the advantage of eliminating the need for daily administration.

Show MeSH
Related in: MedlinePlus