Deletion modification enhances anthrax specific immunity and protective efficacy of a hepatitis B core particle-based anthrax epitope vaccine.
Protective antigen (PA) is one of the major virulence factors of anthrax and is also the major constituent of the current anthrax vaccine. Previously, we found that the 2β2-2β3 loop of PA contains a dominant neutralizing epitope, the SFFD. We successfully inserted the 2β2-2β3 loop of PA into the major immunodominant region (MIR) of hepatitis B virus core (HBc) protein. The resulting fusion protein, termed HBc-N144-PA-loop2 (HBcL2), can effectively produce anthrax specific protective antibodies in an animal model. However, the protective immunity caused by HBcL2 could still be improved. In this research, we removed amino acids 79-81 from the HBc MIR of the HBcL2. This region was previously reported to be the major B cell epitope of HBc, and in keeping with this finding, we observed that the short deletion in the MIR not only diminished the intrinsic immunogenicity of HBc but also stimulated a higher titer of anthrax specific immunity. Most importantly, this deletion led to the full protection of the immunized mice against a lethal dose anthrax toxin challenge. We supposed that the conformational changes which occurred after the short deletion and foreign insertion in the MIR of HBc were the most likely reasons for the improvement in the immunogenicity of the HBc-based anthrax epitope vaccine.
Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, China.
Ying
Y
Yin
Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, China; Department of Pediatrics, BaYi Children's Hospital of The General Military Hospital of Beijing PLA, 5 Nanmencang Road, Dongcheng District, Beijing 100700, China.
Sheng
S
Zhang
Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, China.
Chenguang
C
Cai
Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, China.
Jun
J
Zhang
Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, China.
Dayong
D
Dong
Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, China.
Qiang
Q
Guo
Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, China.
Ling
L
Fu
Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, China. Electronic address: xujunjie1@gmail.com.
Junjie
J
Xu
Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, China. Electronic address: cw0226@foxmail.com.
Wei
W
Chen
D000818:Animals; D000881:Anthrax / Q000276:immunology*; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000917:Antibody Formation / Q000235:genetics; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005822:Genetic Vectors; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism*
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; C030325:anthrax toxin
Anthrax; Deletion modification; Epitope vaccine; HBV; HBc; HBc-N144; HBc-N144-PA-loop2; HBcAg; HBcL2; LeTx; Lethal toxin; MIR; Major immunodominant region; N-terminal 144 amino acids of HBc; PA; VLP; aa; amino acid(s); hepatitis B virus; hepatitis B virus core antigen; hepatitis B virus core protein; major immunodominant region; protective antigen; rLF; rPA; recombinant lethal factor; recombinant protective antigen; virus like particle