Cross‐protection in mice infected with influenza A virus by the respiratory route is correlated with local IgA antibody rather than serum antibody or cytotoxic T cell reactivity

Abstract

Mice previously infected with an aerosol of A/Rec 31 influenza virus were strongly protected against an aerosol challenge with A/Vic influenza as judged by lung virus titers recovered 2 days after the challenge infection. Such complete homotypic immunity was not achieved by priming with live Rec 31 virus injected i.v. or UV-inactivated Rec 31 virus administered s.c. together with Al(OH)3 and saponin. The reason for the superior protective effect of the natural infection was investigated. The protection induced by respiratory infection with Rec 31 virus was specific for influenza A viruses. It was not correlated with specific serum hemagglutination inhibition antibody titer or cross-reactive cytotoxic T (Tc) cell reactivity. Moreover, the transfer of splenic and lymphoid T cell populations with strong secondary Tc activity did not significantly reduce lung virus titers in recipient mice 3 days after infection. The protection however occurred in parallel with the presence of cross-reactive IgA antibody in the lung washings. It thus appears that local secretory IgA plays a causal role in the prevention of cross-infection by influenza A virus. Serum antibody and Tc cells, on the other hand, may be crucial for recovery from such infection. All mice primed with live Rec 31 virus, administered i.v. or by aerosol and expressing equally high levels of Tc reactivity, survived a lethal challenge with A/PR8 virus. The same challenge, however, killed half of the mice immunized s.c. with inactivated Rec 31 virus which induced only a low level of Tc reactivity.

Efficacy of intranasal administration of a truncated NS1 modified live influenza virus vaccine in swine

“…values for IgA in the BALF, further suggesting the importance of cross-reactive IgA for Het-I at the respiratory mucosa. In mice, cross-reactive IgA induced by natural infection was shown to be strongly correlated to protection from challenge with a heterologous homotypic virus [35]. Serum HI antibody titer and cross-reactive cytotoxic T-lymphocytes were not correlated with protection from infection, but instead were related to recovery [35].…”

“…Virus was not detected from any pigs in this group at any time point and macroscopic and microscopic lesions were both significantly reduced to minimal or undetectable levels. Live challenge and recovery or natural exposure to influenza virus has been well documented to have improved Het-I over inactivated vaccines [35][36][37][38]. To demonstrate the ability of the NS1 deletion mutant in inducing Het-I, vaccinated pigs were challenged with a heterologous H3N2 and a heterosubtypic rH1N1.…”

“…In mice, cross-reactive IgA induced by natural infection was shown to be strongly correlated to protection from challenge with a heterologous homotypic virus [35]. Serum HI antibody titer and cross-reactive cytotoxic T-lymphocytes were not correlated with protection from infection, but instead were related to recovery [35]. In addition, IgA was shown to be more cross-reactive than IgG against heterologous virus, and passive transfer of IgA to non-immune mice conferred protection [39], whereas mucosal administration of anti-IgA to immune mice blocked protection from re-infection with the same virus [40].…”

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

“…Indeed, it has been demonstrated in the mouse model that passive transfer of immunoglobulins protect against challenge with infectious influenza virus (Virelizier et al, 1976(Virelizier et al, , 1979. In addition the study of immunoglobulin isotypes stimulated by the inoculation of different virus preparations (Liew et al, 1984) has attempted to examine the antibody isotype involved in these protection mechanisms (Balkovic et al, 1987). With its widespread occurrence in the bloodstream, lymphatics and peripheral body fluids the antibody isotype IgG is likely to be the most important in neutralizing the virus (Possee et al, 1982).…”

Heterosubtypic Immunity to Influenza A Virus in Mice Lacking IgA, All Ig, NKT Cells, or γδ T Cells

“…Foster nursing can confer homosubtypic protection, supporting a role for secretory IgA (14). Some reports have suggested that IgA in secretions may be more cross-reactive than IgG (15)(16)(17)(18)(19); such cross-reactivity may be a mechanism through which IgA could contribute to heterosubtypic immunity. Interference with viral replication or assembly during transcytosis (20,21), as suggested for rotavirus (22), is a potential mechanism that might be mediated by IgA Abs to conserved internal proteins.…”