Low pH, caprylate incubation as a second viral inactivation step in the manufacture of albumin. Parametric and validation studies.

Caprylate has long been used as a stabiliser for albumin solutions, as well as a precipitation agent for immunoglobulins, ceruloplasmin and more recently in removing contaminants during albumin purification. Its virucidal properties have been explored and it has been proposed that the non-ionised form of the caprylate acid disrupts the integrity of the lipid bilayer and membrane associated proteins of enveloped viruses. The studies reported here further explore the use of this fatty acid to inactivate lipid-enveloped viruses in albumin manufactured for therapeutic use. Caprylate concentrations considered above solubility limits were adopted. Acidic pH was used to maximise the percentage of non-ionised caprylate and elevated temperatures were used to enhance inactivation rates. Parameters were manipulated to determine the relationship between pH, temperature and caprylate: protein ratio. These studies demonstrated that elevated temperature and low pH were critical in achieving significant reduction in virus infectivity and that the rate and extent of inactivation was sensitive to changes in caprylate:protein ratio and to changes in pH. Final inactivation conditions of 10% w/v protein, 16 mM caprylate, pH 4.5 and 30 degrees C were chosen to minimise protein dimerisation and to achieve greater than 4 log(10)inactivation of the most resistant virus tested, bovine viral diarrhoea virus. Validation studies using both model and relevant blood borne viruses demonstrated this to be a robust and effective viral inactivation step and is complementary to the commonly used pasteurisation viral inactivation step, thus providing an additional margin of safety to this valuable therapeutic blood product.

Immunity to poliomyelitis in Victorians.

OBJECTIVES: In view of WHO's goal for poliomyelitis eradication by 2005 and the possible introduction of IPV into the Australian Standard Vaccination Schedule, this investigation was conducted to assess current immunity to poliomyelitis across the Victorian community. METHODS: 1,775 sera collected from three population samples within the Victorian community between 1990 and 1995 were tested for neutralising antibody titres against each poliovirus type in accordance with WHO recommended procedure. RESULTS: In infants over three months and adults under 40 years, 76-100% of people in each age group were seropositive to all poliovirus types, with 90-100% seropositive to type I, 94-100% seropositive to type II and 80-97% seropositive to type III. Of the very small number of adults over 40 years tested (n = 13), 85% were seropositive to each of types I and II, and 62% to type III. 92% of vaccination histories taken and checked were confirmed, and reported immunisation rates were significantly below seropositive rates. CONCLUSIONS: According to poliovirus antibody seroprevalence, current immunity to poliomyelitis appears sufficient for herd immunity. When compared with vaccination histones, significantly more people demonstrated immunity to poliomyelitis than the number who reported having been vaccinated against it, indicating the possible role of intestinal vaccine strain poliovirus spread in maintaining high immunity levels. IMPLICATIONS: The current Australian Standard Vaccination Schedule has successfully provided protective levels of poliomyelitis immunity for the Victorian community in the absence of wild virus since at least 1972. This must be considered in assessing the future direction of Australia's poliomyelitis immunisation program.