The Immunoglobulin G Subclass Responses of Mice to Influenza A Virus: the Effect of Mouse Strain, and the Neutralizing Abilities of Individual Protein A-purified Subclass Antibodies

Abstract

SUMMARYThe IgG subclass responses to cold-adapted (ca) influenza A/Queensland/6/72 virus and purified haemagglutinin H3 was assessed in C57BL/6 and BALB/c mice. In BALB/c mice IgG2a was present as the major subclass in serum, lung and salivary secretions after two doses of ca virus. In contrast, the serum response in C57BL/6 mice was predominantly IgG1 after primary and secondary inoculations of ca virus. However, in lung and salivary secretions no specific subclass was dominant. When purified H3 was used as the inoculum, serum responses were dominated by IgGl in BALB/c mice after two inoculations whereas all four subclasses were present at equal levels in C57BL/6 mice. Overall the lung and salivary responses detected in C57BL/6 mice were lower than those observed in BALB/c mice with all four subclasses contributing equally to the response in BALB/c mice. The neutralizing and haemagglutination inhibition abilities of the four Protein A-Sepharose-purified IgG subclasses differed between the BALB/c, C57BL/6 and CBA/CaH mice strains. IgG1 and IgG2a were most effective in BALB/c mice and in C57BL/6 and CBA/CaH mice, IgG2a and IgG2b. These results are discussed in terms of the differing abilities of replicating and non-replicating virus to stimulate differential responses in mice and the TH1 and TH2 helper cell concept.

Calcium Phosphate Nanoparticle Adjuvant

“…In the 1980s several groups reported that IgG2a was the major antibody isotype conferring protection against viral infection and the most effective isotype for the induction of macrophage immunity in mice (1,2,8,10,19). Further studies confirmed that gamma interferon, which is induced by the type 1 CD4 ϩ Th1 response, stimulated the expression of IgG2a and inhibited the production of IgE.…”

Analysis of a recombinant dengue-2 virus-dengue-3 virus hybrid envelope protein expressed in a secretory baculovirus system.

“…The reason for the discrepancy between the results of Smucny et al (1995) and those of the present study is not entirely clear, but three possibilities could be considered. Firstly, the strain of mice used and secondly the age of the animals are both factors known to influence the murine antibody response due to biased T helper cell stimulation (Barrios et al, 1996 ;Hocart et al, 1989). Thirdly, there is increasing evidence to suggest that the dose of antigen, perhaps more than any other single factor, influences the cytokine profile of both naı$ ve (primary response) and differentiated (secondary response) T cells (Bretscher et al, 1992 ;Constant et al, 1995 ;Hosken et al, 1995), and thus, through cognate B cell-T cell interactions, the regulation of immunoglobulin isotype synthesis, including levels and specificities (Coffman et al, 1993).…”

Increased Efficacy of the Immunoglobulin G2a Subclass in Antibody-Mediated Protection against Lactate Dehydrogenase-Elevating Virus-Induced Polioencephalomyelitis Revealed with Switch Mutants

“…However, relatively few studies have compared the protective abilities of the different antiviral antibody IgG subclasses. Whereas some authors have shown that, in their models, the protection did not depend upon the IgG subclass of the antiviral antibodies (1,9,17,24), others, using either polyclonal antibodies or unrelated monoclonal antibodies, have observed that IgG2a displayed a stronger effect (2,13,18,21,28). However, differences in specificity and/or affinity could account for variations in neutralizing ability.…”