Vaccination with hemagglutinin or neuraminidase DNA protects BALB/c mice against influenza virus infection in presence of maternal antibody

Abstract

Background: Maternal antibody is the major form of protection against disease in early life; however, its presence interferes with active immunization of offspring. In order to overcome the immunosuppression caused by maternal antibody, several immune strategies were explored in this paper using mouse model and influenza vaccines.

Results: The results showed that: i) when the offspring were immunized with the same vaccine as their mothers, whether inactivated or DNA vaccine, the presence of maternal antibody inhibited offspring immune response and the offspring could not be protected from a lethal influenza virus infection; ii) when the offspring, born to mothers immunized with inactivated vaccine, were immunized with NA DNA vaccine, the interference of maternal antibody were overcome and the offspring could survive a lethal virus challenge; iii) when the offspring were immunized with different DNA vaccine from that for their mothers, the interference of maternal antibody were also overcome. In addition, high-dose inactivated vaccine in maternal immunization caused partial inhibition in offspring when the offspring were immunized with HA DNA vaccine, while lower dose caused no significant immunosuppression.

Conclusion: To avoid the interference of maternal antibody in influenza vaccination of offspring, mothers and their offspring shall not be immunized with the same vaccine. If mothers are immunized with inactivated vaccine, NA DNA vaccine for the offspring shall be effective; and if mothers are immunized with HA (NA) DNA, NA (HA) DNA for the offspring shall be effective.

Figure 1

Survival of offspring after lethal A/PR8/34 virus challenge. The offspring were vaccinated as described in result section. One week after second immunization, the offspring were challenged with a lethal dose of A/PR/8/34 (20 × LD₅₀). Survival rates of mice were measured after viral challenge. Panel A: (A1) Immunization of both mothers and the offspring with 1.0 μg of inactivated vaccine; (A2) Immunization of both mothers and the offspring with 0.1 μg of inactivated vaccine; (A3) Immunization of both mothers and the offspring with 0.01 μg of inactivated vaccine; (A4) Immunization of offspring born to unimmunized mothers with 1.0 μg of inactivated vaccine; (A5) Immunization of offspring born to unimmunized mothers with 0.1 μg of inactivated vaccine; (A6) Immunization of offspring born to unimmunized mothers with 0.01 μg of inactivated vaccine; (A7) Negative control. Panel B: (B1)Immunization of both mothers and the offspring with 30 μg of HA DNA; (B2) Immunization of offspring born to unimmunized mothers with 30 μg of HA DNA; (B3) Immunization of both mothers and the offspring with 30 μg of NA DNA; (B4) Immunization of offspring born to unimmunized mothers with 30 μg of NA DNA; (B5) Negative control. Panel C: (C1) Immunization of mothers with1.0 μg of inactivated vaccine and the offspring with 30 μg of HA DNA; (C2) Immunization of mothers with 0.1 μg of inactivated vaccine and the offspring with 30 μg of HA DNA vaccine; (C3) Immunization of mothers with 0.01 μg of inactivated vaccine and the offspring with 30 μg of HA DNA; (C4) Immunization of mothers with 1.0 μg of inactivated vaccine and the offspring with 30 μg of NA DNA; (C5) Immunization of mothers with 0.1 μg of inactivated vaccine and the offspring with 30 μg of NA DNA; (C6)Immunization of mothers with 0.01 μg of inactivated vaccine and the offspring with 30 μg of NA DNA; (C7) Negative control. Panel D: (D1) Immunization of mothers with 30 μg of HA DNA and the offspring with 30 μg of NA DNA; (D2) Immunization of mothers with 30 μg of NA DNA and the offspring with 30 μg of HA DNA; (D3) Negative control. *Significant differences (p < 0.05) compared to negative controls as determined by Log Rank test.