Passive broad-spectrum influenza immunoprophylaxis.

Influenza is a perennial problem affecting millions of people annually with the everpresent threat of devastating pandemics. Active prophylaxis by vaccination against influenza virus is currently the main countermeasure supplemented with antivirals. However, disadvantages of this strategy include the impact of antigenic drift, necessitating constant updating of vaccine strain composition, and emerging antiviral drug resistance. The development of other options for influenza prophylaxis, particularly with broad acting agents able to provide protection in the period between the onset of a pandemic and the development of a strain specific vaccine, is of great interest. Exploitation of broad-spectrum mediators could provide barricade protection in the early critical phase of influenza virus outbreaks. Passive immunity has the potential to provide immediate antiviral effects, inhibiting virus replication, reducing virus shedding, and thereby protecting vulnerable populations in the event of an impending influenza pandemic. Here, we review passive broad-spectrum influenza prophylaxis options with a focus on harnessing natural host defenses, including interferons and antibodies.

Modulation of innate immune responses by influenza-specific ovine polyclonal antibodies used for prophylaxis.

In the event of a novel influenza A virus pandemic, prophylaxis mediated by antibodies provides an adjunct control option to vaccines and antivirals. This strategy is particularly pertinent to unvaccinated populations at risk during the lag time to produce and distribute an effective vaccine. Therefore, development of effective prophylactic therapies is of high importance. Although previous approaches have used systemic delivery of monoclonal antibodies or convalescent sera, available supply is a serious limitation. Here, we have investigated intranasal delivery of influenza-specific ovine polyclonal IgG antibodies for their efficacy against homologous influenza virus challenge in a mouse model. Both influenza-specific IgG and F(ab')2 reduced clinical scores, body weight loss and lung viral loads in mice treated 1 hour before virus exposure. Full protection from disease was also observed when antibody was delivered up to 3 days prior to virus infection. Furthermore, effective prophylaxis was independent of a strong innate immune response. This strategy presents a further option for prophylactic intervention against influenza A virus using ruminants to generate a bulk supply that could potentially be used in a pandemic setting, to slow virus transmission and reduce morbidity associated with a high cytokine phenotype.

A skin chamber to investigate wound infection and healing in the mouse.

  The development of a simple, convenient, and reliable polypropylene screw-capped skin chamber, which can be inserted into mice, is described. All implanted chambers of normal immuno-competent mice (n = 10), or immuno-suppressed mice (n = 10) remained in-situ for 15 days. Wound infection was established by a clinical isolate of Pseudomonas aeruginosa in immuno-competent mice (n = 10) 1 day after chamber implantation and chambers remained in-situ for 10 days. Similar infections of wounds among mice immuno-suppressed with cyclophosphamide resulted in the mouse becoming moribund due to systemic invasion by the bacterium. The authors conclude that this mouse skin chamber will be of potential value for studying wound healing during the inflammatory and early proliferative phases, and the influence of infection and treatments on these processes in immuno-suppressed and immuno-competent mice.