Enhanced Immunogenicity in Mice of a Purified, Tween-Ether-Treated Influenza Vaccine

Abstract

The immunogenic response of mice vaccinated intranasally or subcutaneously with increasing doses of a purified, concentrated intact A2/Taiwan influenza vaccine or its Tween-ether derived vaccines was compared. Immunogenicity was measured by serum neutralization and hemagglutination-inhibition antibodies, lung lesions scores, and protection against respiratory challenge with live airborne influenza virus. Intact (untreated) vaccine, Tween-ether-treated (ET) vaccine, and the isolated hemagglutinins (HA) provided protection and stimulated homologous antibody response at the 35-and 70-chicken cell agglutination (CCA) unit level. At a lower dosage level, the vaccines administered by the subcutaneous route appeared to confer better protection. The ET vaccine was superior to intact virus or HA vaccines when administered subcutaneously. The minimum amount of the HA and intact vaccine given subcutaneously that protected mice against respiratory challenge was 7 CCA units (3.5 units injected twice) compared to 0.7 CCA units (0.35 units injected twice) for the ET vaccine. No heterologous antibody to the A/PR/8/34 or B/Mass/3/66 was noted. Low-level serum-neutralizing antibody was found against the A2/Japan/170 strain but, despite high levels of homologous A2/Taiwan/64 antibody, no cross-reactivity was found with the recent A2/Hong Kong/68 variant.

Superior Immunogenicity of Inactivated Whole Virus H5N1 Influenza Vaccine is Primarily Controlled by Toll-like Receptor Signalling

“…H5N1 virus (NIBRG-14, a 2∶6 recombinant of A/Vietnam/1194/2004 [H5N1] and A/PR/8/34 [H1N1] virus produced by reverse genetics technology) was provided by the National Institute for Biological Standards and Controls (NIBSC; Potters Bar, UK), propagated on embryonated chicken eggs, inactivated with 0.1% β-propiolactone to obtain WIV, and processed into split virus vaccine or subunit vaccine according to standard procedures [37] , [38] . The haemagglutinin protein concentration in the vaccines was determined by single radial immunodiffusion (SRID) [39] .…”

Inactivated Influenza Vaccine Efficacy: Diminished Antigenicity of Split-Product Vaccines in Mice

“…Currently, the potency of these vaccines is measured by the chick cell agglutination (CCA) test (20), which directly quantitates only the hemagglutinin component of the virus. Although the test is relatively precise and reproducible when values obtained for a given vaccine are compared with a standard reference (37), previous experiments have shown that differing egg passages (19) and various manufacturing procedures (5,12,23,31,35) might alter the relationship between the immunogenicity of influenza vaccines and their CCA content. Techniques that quantitate the immunogenic potential of vaccines in experimental animals by antigen extinction methods have therefore been suggested (27,35) as more relevant in determining the protective capacity of inactivated vaccines.…”

“…IMMUNITY cines (18). Previous experiments on the protective efficacy of experimentally produced "splitproduct" influenza vaccines in mice were somewhat contradictory (5,12,23), whereas earlier experience with inactivated measles vaccines subjected to ether treatment had shown them to be, in some respects, less immunogenic than equivalent whole-virus vaccines (24,25). This investigation was designed, therefore, to elucidate any differences that may exist between the immunogenic capacity, in large groups of mice, of whole-virus and split-product influenza vaccines.…”