Immunoglobulin A (
IgA) is the primary immune response induced in the intestine by
rotavirus infection, but vaccination with virus-like particles induces predominantly
IgG, not
IgA. To definitively assess the role of
IgA in protection from
rotavirus infection,
IgA knockout mice, which are devoid of serum and
secretory IgA, were infected and then rechallenged with murine rotavirus at either 6 weeks or 10 months. Following primary
rotavirus infection,
IgA knockout mice cleared virus as effectively as
IgA normal control mice. Rotavirus-infected
IgA knockout mice produced no serum or fecal
IgA but did have high levels of antirotavirus serum
IgG and
IgM and fecal
IgG, whereas
IgA normal control mice made both serum
IgA and
IgG and fecal
IgA. Both
IgA normal and
IgA knockout mice were totally protected from rotavirus challenge at 42 days. Ten months following a primary
infection, both
IgA normal and knockout mice still had high levels of serum and fecal antirotavirus antibody and were totally protected from rotavirus challenge. To determine if compensatory mechanisms other than
IgG were responsible for protection from
rotavirus infection in
IgA knockout mice, mice were depleted of CD4(+) T cells or CD8(+) T cells. No changes in the level of protection were seen in depleted mice. These data show that fecal or systemic
IgA is not essential for protection from
rotavirus infection and suggest that in the absence of
IgA,
IgG may play a significant role in protection from mucosal pathogens.