Correlation of Laboratory Studies with Clinical Responses to A/New Jersey Influenza Vaccines

Abstract

The large, uniformly performed clinical investigations with influenza A/New Jersey vaccines provided an opportunity to correlate results of laboratory tests of vaccine with human reactivity and antibody responses. These vaccines were given to large numbers of subjects under code, and significant differences in immunogenicity and reactivity were observed in unprimed individuals. A single, relatively large dose of intact virus was more immunogenic and reactive than split-virus vaccines in unprimed subjects. Differences in immunogenicity and reactivity in unprimed subjects correlated with the amount of intact virus in the vaccines (measured by column chromatography or electron microscopy) and with the amount of viral hemagglutinin in the vaccine (measured by immunodiffusion), but not with the number of chick cell-agglutinating units.

Protection against experimental infection with influenza virus A/equine/Miami/63 (H3N8) provided by inactivated whole virus vaccines containing homologous virus

“…In the present study, the serological data demonstrated a clear relationship between vaccine potency (#g HA/dose) and levels of antibody stimulated by one and two doses of vaccine, confirming previous observations (Wood et al 1983a) that the SRD technique (Wood et al 1983b) (Ennis et al 1977;Nicholson et al 1979) and protection (Goodeve, Jennings & Potter, 1983;Al-Khayatt, Jennings & Potter, 1984) are related to vaccine SRD potency. The 100 % protective levels of SRH antibody for influenza H3N2, HINI and B infections were in the region of 90 mm2.…”

Standardisation of inactivated influenza vaccines—Learning from history

“…From international collaborative studies, the results of CCA assays were seen to vary between laboratories by up to twofold5 and with the advent of split virus and subunit vaccines, the CCA assay proved to be unreliable and not a good indicator of immunogenicity in humans. This was dramatically demonstrated during the “swine flu” A/New Jersey/76 (H1N1) vaccine trials in 1976, where the CCA values of newly developed split vaccines did not correlate with immunogenicity 6, 7…”

“…The SRID assay measured the concentration of haemagglutinin (HA) in influenza vaccines by virtue of its reaction with specific antibody to produce precipitin rings in an agarose gel, whereas the IEP assay utilised an electrophoretic current to elongate the precipitin rings into rocket‐shaped peaks. When SRID assays were used to test the “swine flu” vaccines in 1976, there was an excellent correlation between antigen content and vaccine immunogenicity, irrespective of whether the vaccine was whole virus, split virus or subunit 6, 7. However, this was not the case for the IEP assay, but more of that later.…”

“…The SRID assay measures the quantity of HA by means of its reaction with specific antibody and has been shown to correlate with vaccine immunogenicity, first in the H1N1 vaccine trials during the late 1970s6, 7, 12 and in numerous vaccine clinical trials since then.…”

Validation of alternative potency assays for influenza vaccines requires clinical studies

“…SRID was developed and "validated" in the 1970s as an alternative to the gold-standard method at the time, Chick Cell Agglutination (CCA), which was commonly acknowledged as a relatively poor indicator of vaccine potency. The seminal validation study for SRID was published by Ennis, et al in 1977. In that work, the immunogenicity of a monovalent A/New Jersey/8/76 vaccine as measured by hemagglutination inhibition (HI) in a clinical study of 2326 young adults was compared to the protein content in the vaccine as determined by CCA and SRID, as well as other methods. The top panel of Fig.…”