Immunogenicity of a monovalent, aluminum-adjuvanted influenza whole virus vaccine for pandemic use.

In the case of an influenza pandemic a significant gap between influenza vaccine manufacturing capacities and vaccine demands must be expected on a global scale. This study explores the possibility to increase the number of vaccine doses that can be provided with the existing resources by using a lower amount of antigen per dose in an aluminum-adjuvanted whole virus vaccine formulation, instead of the standard dosage of 15 microg hemagglutinin (HA). The study was performed as an open, non-controlled, randomized, multicentric study in 200 volunteers (18-30 years of age). Three monovalent aluminum-adjuvanted whole virus formulations with different antigen concentrations (1.9, 3.75 and 7.5 microg HA per dose) were compared to a split virus vaccine (15 microg HA per dose) without aluminum adjuvantation. The sera were tested for hemagglutination inhibition (HI) antibodies, neuraminidase inhibition (NI) antibodies and virus neutralizing (VN) antibodies. Nasal swab samples were tested for influenza-specific IgA antibodies. All volunteers were immunologically naïve to the vaccine strain influenza A/Singapore/1/57 (H2N2). The vaccine was well tolerated. HI titers reached protective levels (geometric mean titer (GMT) >1:40) after two vaccine doses. In the group immunized with the lowest antigen dose the seroprotection rate was 82%. Although the immune response tends to be lower for vaccine formulations with reduced antigen content, the immunogenicity criteria as defined by the European Agency for the Evaluation of Medicinal Products (EMEA) were met with all antigen formulations after two vaccine doses. Significant increases in HI, NI and VN titers were observed, however, no significant local immune response was detected. The use of a low-dose whole virus influenza vaccine, adjuvanted with aluminum appears to be a viable approach to increase vaccine supplies in a pandemic situation.

Pandemic preparedness: lessons learnt from H2N2 and H9N2 candidate vaccines.

Vaccination against influenza is considered to be one of the key interventions in case of a pandemic. Unfortunately, shortages in vaccine supplies will occur because of the substantial increase in vaccine demands worldwide and the limited available supply resources. The recommended use of monovalent--instead of current trivalent--vaccines containing 15 micro g hemagglutinin (HA) per dose can theoretically triple vaccine volumes but is unlikely to meet the demand. Furthermore, previous experiences demonstrated that one dose of 15 micro g HA will not be sufficient to elicit protective antibody levels in unprimed individuals. Modified formulation approaches were investigated, that would be suitable to provide significantly higher volumes of potent vaccine within a given period of time. Low doses of HA combined with aluminum (Al) adjuvants and the use of whole virus instead of split or subunit antigens can lead to substantial increases in process yield. In addition, production of whole virus vaccines will reduce manufacturing complexity. In a dose-finding study in healthy adults and elderly, immune responses after administration of Al-adjuvanted low-dose formulations were compared to a standard split virus vaccine (Fluarix, GlaxoSmithKline Biologicals, Rixensart, Belgium). All vaccines were safe and well tolerated. Antigen concentrations as low as 1.9 micro g HA/strain per dose of adjuvant-containing experimental vaccines induced protective antibody levels in primed populations. Reactogenicity profiles of Al-adjuvanted low-dose vaccines were investigated in a feasibility trial. Neither the use of Al-adjuvant nor of whole virus had a significant effect on general reactions. Studies in unprimed populations with H2N2 and H9N2 candidate vaccines showed different results, with a potential need for a two-dose schedule. Indeed, hemagglutination inhibition titers did not reach protective levels after a single vaccine dose but could be met following administration of a second dose. The same is true for Al-adjuvanted whole virus formulations with an up to eightfold-reduced antigen content. It may be concluded that the use of Al-adjuvanted whole virus vaccines with low HA content can raise protective antibody levels after two vaccine doses, which may, in turn, result in significant increases of vaccine supplies in the case of a pandemic.

[Detection of IgG antibodies against rubella virus using the "Rubella-IgG-EIA SSW" test kit]. / Nachweis von IgG-Antikörpern gegen Röteln-Virus mit dem Testsatz "Rubella-IgG-EIA SSW".

A new commercial ELISA test kit "Rubella-IgG-EIA SSW" is described for the determination of IgG antibodies to rubella virus. A panel of 99 sera was tested by "Rubella-IgG-EIA SSW" and by hemagglutination-inhibition (HI test). The results of enzyme-immunoassay (EIA) and of HI test correlate well; the coefficient of correlation is 0.95, the specificity is 90.9% and the sensitivity is 100%. A coefficient of correlation was found out of 0.92 between EIA and HI test in the evaluation of the quantitative procedure. The test kit can be used for determination of immune status to rubella virus and for quantitative detection of rubella-IgG antibodies.