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. 2013 Jul 9:10:227.
doi: 10.1186/1743-422X-10-227.

An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge

Ji-Hong Ma  1 , Fu-Ru Yang, Hai Yu, Yan-Jun Zhou, Guo-Xin Li, Meng Huang, Feng Wen, Guangzhi Tong
Affiliations

An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge

Ji-Hong Ma et al. Virol J. .

Abstract

Background: Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses.

Results: Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds' adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus.

Conclusions: Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.

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Figures

Figure 1
Figure 1
M2e-specific antibody titers induced by M2e-MAP vaccine. Mice were vaccinated with M2e-MAP plus Freund adjuvant (s. c.). Mice receiving Freund were used as negative controls. Sera were collected at 1, 2, 3, 4 weeks post first immunization. The titers were expressed as the highest serum dilution which is greater than twice the average absorbance value at OD450 nm of pre-vaccination sera. The data are expressed as geometric mean titer (GMT) ± standard deviation (SD) of 10 mice per group. The lower limit detection (1:20) is indicated by a dotted line. Experiments were repeated three times.
Figure 2
Figure 2
Viral amounts in lungs on day 3 post challenge. 5 mice of every challenge group were euthanized 3 days post-challenge and the viral amounts of lungs were determined by real time PCR. The values were expressed as the mean log10 viral copies/μL ±S.D of 5 mice per challenge group. *means in PR8 challenged group P < 0.001 compared to the Freund’s adjuvant control; **means in SwGD96 challenged group P < 0.001 compared to the Freund adjuvant control; ***indicates in SwHLJ1 challenged group P < 0.001 compared to the Freund adjuvant control.
Figure 3
Figure 3
Histopathological changes in the lungs of virus challenged mice. Immunized mice were challenged by PR8 (A and D), SwGD96 (B and E) and SwHLJ1(C and F) and lungs were collected for histopathological analysis 3 days post challenge (HE stain; bar = 50 um).The figure indicates the representative imagines of histopathological observations of M2e-MAP plus Freund immunized mice or Freund only.
Figure 4
Figure 4
Survival curve and body weight in PR8 challenged mice. Survival curve and body weight in PR8 challenged mice. Mice were challenged with 10LD50 of PR8 virus intranasally and monitored daily for 2 weeks post challenge. A. Survival rate. The significant different (P<0.0001) of M2e-MAP+Freund versus Freund alone is indicated as *. B. Percentage (%) of mouse body weight. Each point represents mean of 10 mice per group.
Figure 5
Figure 5
Structure of the synthetic M2e-MAP. The M2e-MAP was synthesized on [Fmoc-Lys (Fmoc)] 2-Lys-Cys (Acm)-βAla-Wang Resin in a tetra-branched form, which carries four copies of M2e, those four copies of M2e were fused to one copy of foreign T helper (Th) cell epitope.
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