Early Protection In Mice Provided By Adjuvanted Inactivated H7N9 Influenza Vaccine

According to the updated data by WHO in Feb.2015,the newly emerging avian influenza A H7N9 virus has resulted in 602 cases of human infection,including 227 deaths.Most of the infections occurred in the mainland of China,with sporadic cases in Hongkong,Taiwan and some neighboring areas.The virus has spread further,and the recent epidemiology surveillance suggested that the virus had the potential to be a pandemic strain.Vaccination is the best method to prevent the influenza virus.It is thought that the body needs 2 or 3 weeks to produce enough special immunity to afford effective protection after vaccination against influenza.What’s the situation about the immune responses in the early time after immunization?Would inactivated influenza vaccine be able to provide an early protection shortly after the immunization?These questions were discussed in this paper by using BALB/c mice as an animal model.Mice were immunized intramuscularly once with different dosages（0.015μg,0.15μg,1.5μg and 15μg）of inactivated whole-virion H7N9vaccine alone or plus MF59 as an adjuvant.Vaccine specific Ig M and Ig G antibody titers in sera of one part of mice in each group were detected by ELISA 3,5,7,14,21,28 days after immunization.To evaluate the early protection provided by the vaccine,another part of mice in each group were challenged with lethal dose(40LD₅₀)of homologous virus 3,5 and7 days,respectively,after the immunization.The survival rates and body weight changes of mice 21 days post-challenge and the residue lung virus titers 3 days post-challenge were determined.Antibody detection by ELISA showed that specific Ig M and Ig G antibody titers in sera of mice increased with the amount of vaccine antigen.The Ig M titers were not low even 3 days after immunization and reach their highest at day 5-7.At day 28 they could not be detectable.On the other hand,the Ig G titers could not be detectable at day 3,but rose quickly over the time and began to flatten from day 21.Specific antibodies increased or significantly increased when the vaccine was adjuvanted with MF59.The early protections provided by the vaccine were evaluated and showed that,when mice were immunized with vaccine alone and were challenged 3 days after immunization,the survival rate of mice increased with the amount of antigen,and was above 50%in both 1.5μg-and 15μg-dosage groups.When challenged 5or 7 days after immunization,mice all survived except those in the0.015μg-dosage group,which had a survival rate over 50%.Addition of MF59 to the vaccine enhanced the early protective abilities.The results demonstrated that mice could obtain effective protection 3 day after immunization with the inactivated H7N9 vaccine at a high dosage,and5-7 days after immunization even at a low dosage.Thus it could be concluded that early immune responses induced by the vaccine provided effective protection.The study would be useful for vaccination against influenza.In addition,apart from the above main study,immune protections provided by inactivated whole-virion vaccine and split vaccine with or without an adjuvant（including Al（OH）₃,poly（I:C）,Cp G and PEI）were compared in the mouse model.The results showed that,when the two types of vaccines were injected at the same HA dosage（0.015μg）,the protective ability by the split vaccine alone was 33.3%,and by the whole-virion vaccine alone was 90%.Except for the whole-virion vaccine+poly（I:C）combination,which exhibited no adjuvant effect,all other combinations provided 100%protection against challenge.The whole-virion vaccine+Al（OH）₃ and split vaccine+Cp G were the two best combinations,which demonstrated that the effect of an adjuvant were influenced by the type of vaccine to some extent.