Clin Exp Vaccine Res.  2014 Jul;3(2):194-201. 10.7774/cevr.2014.3.2.194.

Assessment of mOMV adjuvant efficacy in the pathogenic H1N1 influenza virus vaccine

• Lee BJ
• Kwon HI
• Kim EH
• Park SJ
• Lee SH
• Choi YK
• Kim SH

• KMID: 1730624
• DOI: http://doi.org/10.7774/cevr.2014.3.2.194

Abstract

PURPOSE
Since the pandemic (H1N1) 2009 virus has been a seasonal flu which still poses great human health concerns worldwide, vaccination would be considered as the most effective strategy to control the influenza virus spreading. Here, we assessed adjuvant efficacy of modified outer membrane vesicle (mOMV) towards the pandemic H1N1 split antigen.
MATERIALS AND METHODS
For this study, mice were vaccinated twice with various amount of antigen (0.05, 0.1, and 0.5 microg/dose hemagglutinin [HA]) that were mixed with mOMV, aluminum hydroxide (alum), and MF59, as well as the combined adjuvant comprising the mOMV plus alum.
RESULTS
We found that all the adjuvanted vaccines of A/California/04/09 (CA04, H1N1) containing HA antigen more than 0.1 microg/dose protected effectively from lethal challenge (maCA04, H1N1) virus, compared to the antigen only group. Furthermore, vaccinated mice received as low as 0.05 microg/dose of the split vaccine containing the combined adjuvant (10 microg of mOMV plus alum) showed a full protection against lethal challenge with H1N1 virus. Taken together, these results suggest that mOMV can exert not only the self-adjuvanticity but also a synergy effect for the vaccine efficacy when combined with alum.
CONCLUSION
Our results indicate that mOMV could be a promising vaccine adjuvant by itself and it could be used as a vaccine platform for development of various vaccine formulations to prepare future influenza pandemic.

Keyword

Influenza A virus; A/California/04/09 (CA04, H1N1); Adjuvant; mOMV

MeSH Terms

Aluminum Hydroxide
Animals
Hemagglutinins
Humans
Influenza A virus
Influenza A Virus, H1N1 Subtype
Influenza, Human
Membranes
Mice
Orthomyxoviridae*
Pandemics
Seasons
Vaccination
Vaccines
Aluminum Hydroxide
Hemagglutinins
Vaccines

Figure

• 

  Fig. 1 Hemagglutination inhibition (HI) titers raised in the mice received the adjuvanted H1N1 split vaccine. Groups of 4-week-old mice were vaccinated twice at a two-week interval with H1N1pdm virus. Sera were collected from peri-orbital sinus after 2 weeks post-vaccination of the last vaccine, and mean HI titers against A/California/04/09 (CA04, H1N1) virus was determined and expressed as the reciprocal of the highest dilution of serum. (A) The antigen only groups at different doses (0.05, 0.1, and 0.5 µg/dose). (B) The modified outer membrane vesicle (mOMV)-adjuvanted groups. (C) The aluminum hydroxide (alum)-adjuvanted groups. (D) The MF59-adjuvanted groups. (E) The mOMV+alum combined adjuvanted groups. The limit of detection for the HI assays done was set to ≤20 HI unites.

• 

  Fig. 2 Body weight change after virus challenge. Body weight was monitored in the vaccinated mice after challenge with A/California/04/09 (maCA04, H1N1) virus for 15 days post-infection. (A) H1N1pdm antigen only groups at different doses (0.05, 0.1, and 0.5 µg/dose). (B) The modified outer membrane vesicle (mOMV)-adjuvanted groups. (C) The aluminum hydroxide (alum)-adjuvanted groups. (D) The MF59-adjuvanted groups. (E) The mOMV+alum combined adjuvanted groups. The monitoring of mice lost their body weight more than 20% was terminated as death. Error bar represents average weight of each group at the indicated day. HI, hemagglutination inhibition.

• 

  Fig. 3 Survival rate of the vaccinated mice after the virus challenge. Survival rate of the booster-vaccinated mice was monitored every day during 15 days post-infection. (A) H1N1 pdm antigen only groups at different doses (0.05, 0.1, and 0.5 µg/dose). (B) The modified outer membrane vesicle (mOMV)-adjuvanted groups. (C) The aluminum hydroxide (alum)-adjuvanted groups. (D) The MF59-adjuvanted groups. (E) The mOMV+alum combined adjuvanted groups.The immunized mice were challenged with lethal dose of A/California/04/09 (maCA04, H1N1) virus. Each point represents the mean body weight of 10 mice per group (n=10).

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