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

Ma JH, Yang FR, Yu H, Zhou YJ, Li GX, Huang M, Wen F, Tong G - Virol. J. (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

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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Related in: MedlinePlus

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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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.

Mentions: A/Swine/Heilongjiang/1/05(SwHLJ1; H3N2), A/Swine/Guangdong/96/06(SwGD96; H1N1)were isolated from China [23,24]. A/Puerto Rico/8/34(PR8; H1N1) is a mouse-adapted virus. Viruses were grown in allantoic fluids of 10-day-old SPF embryonated chicken eggs at 37°C for 3 days. Virus were harvested and stored in aliquots at −80°C. The 50% lethal dose (LD50) of PR8 was determined in mice after serial dilutions of the virus stock and the result was calculated by Reed Muenchmethod [25]. The tetra-branched M2e-MAP was constructed by fusing four copies of a universal sequence which is an extracellular part of M2 protein with one copy of promiscuous T helper (Th) cell epitope [26] by a lysine tree with two additional Lys residues defining a putative cleavage site for cathepsin D [27]. Then it was synthesized by Genscript Co., Ltd (China). The synthesized peptide was prepared at 10 mg/mL in distilled water and stored at −20°C.The structure of M2e-MAP is shown in Figure 5.


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

Ma JH, Yang FR, Yu H, Zhou YJ, Li GX, Huang M, Wen F, Tong G - Virol. J. (2013)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716895&req=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.
Mentions: A/Swine/Heilongjiang/1/05(SwHLJ1; H3N2), A/Swine/Guangdong/96/06(SwGD96; H1N1)were isolated from China [23,24]. A/Puerto Rico/8/34(PR8; H1N1) is a mouse-adapted virus. Viruses were grown in allantoic fluids of 10-day-old SPF embryonated chicken eggs at 37°C for 3 days. Virus were harvested and stored in aliquots at −80°C. The 50% lethal dose (LD50) of PR8 was determined in mice after serial dilutions of the virus stock and the result was calculated by Reed Muenchmethod [25]. The tetra-branched M2e-MAP was constructed by fusing four copies of a universal sequence which is an extracellular part of M2 protein with one copy of promiscuous T helper (Th) cell epitope [26] by a lysine tree with two additional Lys residues defining a putative cleavage site for cathepsin D [27]. Then it was synthesized by Genscript Co., Ltd (China). The synthesized peptide was prepared at 10 mg/mL in distilled water and stored at −20°C.The structure of M2e-MAP is shown in Figure 5.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

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.

Show MeSH
Related in: MedlinePlus