Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice

► We determine if protective immunity against influenza A viruses is higher in females than males. ► We examine humoral immune responses to primary sublethal infection with H1N1 or H3N2 viruses and virus titers and morbidity following secondary lethal challenge with homologous or heterologous virus. ► Females mount higher neutralizing and total anti-influenza A virus antibodies and experience less morbidity and have lower viral titers in their lungs after infection with a lethal dose of heterologous virus. ► Females develop greater cross protection against influenza A viruses than males.