Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant

Abstract

To evaluate humoral (antibody) and cell mediated immune (CMI) responses, 30 healthy young adults were either given inactivated influenza vaccine with or without QS21 adjuvant. Vaccination site pain and postvaccination myalgias were greater in the QS21 group. Serum antibody increases occurred in 73 to 93% of subjects for each vaccine and antigen at 2 weeks and 4 weeks but frequencies and mean titers for the two vaccines were not different. No differences in T cell cytotoxicity were detected for either vaccine for influenza A or B infected cells. IFN-γ for both vaccine groups was increased in supernates after 3 days but not 7 days of stimulation in the cytotoxicity tests; amounts for the two vaccines were similar. To further evaluate CMI, remaining PBMCs were stimulated overnight with cells infected with each vaccine strain; an increase in spot forming cells (sfc) for Granzyme B and IFN-γ was found for all subjects and in 51 of 54 sfc tests. A slightly higher response in the Gran B test for QS21 subjects was suggested, but no clear immune response advantage was identified among healthy adults for QS21 adjuvanted influenza vaccine.

Discordance between antibody and T cell responses in recipients of trivalent inactivated influenza vaccine

“…In high responders post vaccination, IFNγ producing T cells may be responding to the HA and the NA proteins contained in the inactivated vaccine. Recent reports have found a considerable amount of nucleoprotein and M1 protein in the inactivated influenza vaccine; these may be additional targets for CD8 T cell responses [35][36][37]. The presence of high baseline neutralizing antibodies may contribute to the lack of responses in individuals with high baseline numbers of IFNγ producing cells.…”

Selection of Adjuvants for Enhanced Vaccine Potency

“…QS21 did not exert any significant effect on either binding or neutralizing antibody titers after IM immunization of gp120 HIV-1(MN) protein (rsgp120) at doses of 100, 300, and 600 µg, even though it is effective at a lower antigen dose [247]. Similarly, QS21 adjuvant was not effective in enhancing the immunogenicity of an inactivated influenza vaccine in healthy young adults, in terms of serum titers, T cell cytotoxicity, and IFN- levels [248].…”

“…The more purified form QS21 is much better tolerated but the side effects still prevent its use as an effective adjuvant. These side effects include moderate to severe pain for a recombinant HIV protein vaccine [247], site pain and postvaccination myalgias for inactivated influenza vaccine in healthy young adults [248], malaise, headache, fever, and nausea [247]. Two out of 89 subjects developed severe vaccine allergy following the third dose of 1/3 QS21/SPf66 formulations (a synthetic malaria peptide vaccine) [246].…”

Correlates of vaccine protection from influenza and its complications

“…68 Recently, analysis of CMI after vaccination with inactivated influenza vaccine was performed using three different assays. 69 CTL-specific lysis at 2 and 4 weeks after vaccination failed to detect a significant increase in specific cytotoxicity toward either influenza A or B viruses compared with pre-vaccination values, and considerable variability at all timepoints was observed. Interferon (IFN)-c measured in CTL supernatants revealed an initial increase over baseline after three days of stimulation that was not seen at day seven.…”

“…Enzyme-linked immunospot (ELISPOT) analysis of granzyme B and IFN-c expressing cells provided the best indicator of CMI induction. 69 As a correlate of vaccine immunity, a combination of approaches might be needed, with a method to enumerate influenza specific CTLs such as tetramer/pentamer technologies specific to dominant host HLAs, coupled with a functional measure of immunity such as ELISPOT. Due to variability in responses and HLA backgrounds in humans, these correlates are unlikely to be universal, but would at least provide a detectable readout for CTL presence.…”