Cellular Immune Responses in the Murine Lung to Local Immunization with Influenza A Virus Glycoproteins in Micelles and Immunostimulatory Complexes (Iscoms)

Abstract

Primary immunization with a single inoculum of either micelles or iscoms containing influenza A virus glycoproteins failed to induce either B or cytotoxic T (Tc) cell responses. In contrast, immunization with two inocula of iscoms, but not micelles, resulted in the appearance of influenza virus-specific antibody-secreting cells (ASC) but not Tc cells in the lung. There was a 10-fold increase in Tc cell precursor frequency and an increase in ASC generated by secondary in vitro stimulation of lung cell cultures obtained from mice primed with iscoms but not micelles. In mice primed with infectious virus, secondary immunization with either micelles or iscoms increased the number of ASC in the lung and elicited virus-specific Tc cell responses. In contrast homologous virus challenge failed to induce detectable secondary B or Tc cell responses.

The iscom structure as an immune-enhancing moiety: experience with viral systems

“…Intranasal immunization of mice with two doses of 5-pg HANA iscoms elicited antibody titres (IgM, IgG and IgA) comparable to those elicited by virus infection (Jones et al, 1988 and. Furthermore, virus-specific antibody-secreting cells could be demonstrated in the lungs.…”

“…Both iscoms and micelles induced CTL precursors in the lungs of mice but the levels were four-fold higher in iscom-immunized mice. Natural killer cells were found in similar quantities after immunization with either of the antigen preparations (Jones et al, 1988). Complete protection of mice against intranasal challenge with influenza virus could be induced by intranasal and subcutaneous immunizations with HANA iscoms (Sundquist et al, 1988 andLovgren et al, 1990).…”

“…No systemic antibody response could be measured and it was speculated that iscoms could not resist degradation in the gastrointestinal tract. Intranasal immunization with influenza virus iscoms, however, led to a specific antibody response of all classes and subclasses, including IgA, and also to cellular responses in the lung (Jones et a/., 1988). This showed that local immunization with iscoms may lead to the induction of both local and systemic immune responses.…”

“…In general, non-replicating antigens do not enter the cytosolic pathway, so that no priming for MHC class-I-restricted CTL occurs. The ability of iscoms to stimulate CDS+ CTL in vivo has been demonstrated with different iscom preparations (Jones et al, 1988;Takahashi et al, 1990;Trudel et al, 1992), even after oral immunization (Mowat and Donachi, 1991). In our laboratory, data have been generated which show that iscoms can stimulate MHC class-I-specific CTL in vitro (van Binnendijk et al, submitted) and in vivo (Claassen et al, submitted).…”

“…Quil A is a necessary constituent of the iscom structure. The size and morAntigen nature Name Mowatt et al, 1991a/b Lovgren et al, 1987Erturk et al, 1989Trudel et al, 1987, 1988Wahren et al, 1987Tsuda et al, 1991Morgan et al, 1988Howard et al, 1987Trudel et al, 1988Carlson et al, 1991De Vries et al, 1988aDe Vries et al, 1988bVisser et al, 1989Trudel et al, 1989Trudel et al, 1992Fedaku et al, 1992Jones et al, 1988Merza et al, 1991Osterhaus et al, 1992Takehashi et al, 1990Pyle et al, 1989Nagy et al, 1990Winter et al, 1988…”