Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection

Abstract

Maternally-derived antibodies (MDAs) can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP) or intranasal (IN) route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN) was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition.

Fig 1. Body weight changes in the offspring within 21 days after the lethal virus challenge.

A). Both mothers and offspring were immunized with the inactivated vaccine through the IP route. B). Mothers were immunized through the IP route and offspring through the IN route. C). Both mothers and offspring were immunized through the IN route. D). Mothers were immunized through the IN route and offspring through the IP route. Data points represent the means ± SD of each group of mice. “MDA- control” indicates that the offspring in this group had no MDAs and were unimmunized; “1μg MDA+” indicates that the offspring in this group had MDAs and were immunized with 1 μg of the vaccine.

Fig 2. Survival rates of offspring over time after lethal virus challenge.

A). Both mothers and offspring were immunized with the inactivated vaccine through the IP route. B). Mothers were immunized through the IP route and offspring through the IN route. C). Both mothers and offspring were immunized through the IN route. D). Mothers were immunized through the IN route and offspring through the IP route. Data points represent the means ± SD of each group of mice. “MDA- control” indicates that the offspring in this group had no MDAs and were unimmunized; “1μg MDA+” indicates that the offspring in this group had MDAs and were immunized with 1 μg of the vaccine. ^aSignificant differences (p < 0.05) compared with the MDA- control determined by the Log Rank test.