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Table 2 Some examples of M2e-based vaccines

From: M2e-based universal influenza vaccines: a historical overview and new approaches to development

Carrier Animals Immunization route* Main results Reference
Hepatitis B virus core protein Mice IP+ or IN 3 immunizations at 3-week intervals with 5, 10, or 50 μg led to the formation of M2e-antibodies in mice. Groups immunized with 10 μg IP and IN in subsequent vaccination studies were protected after challenge with 5 LD50 of A/PR/8/34 (H1N1) and A/Victoria/3/75 (H3N2). The significant role of M2e antibodies in passive transfer experiments was shown. [88]
Mice IM+ 3 immunizations at 2-week intervals with 50 μg induced high levels of M2e-antibodies. Challenge with 5 LD50 of different heterologous viruses showed high degree of protection. [122]
Modified form of the leucine zipper of the yeast transcription factor GCN4 Mice IP+ or IN+ 3 immunizations with 10 μg doses led to the formation of specific IgG1 and IgG2a M2e antibodies. The tetrameric M2e-tGCN4 vaccine induced M2e-specific IgG antibody that recognized natural M2 ectodomain. Immunized mice were fully protected against challenge with 4 LD50 X47. [17]
Prime with M2-DNA and boost with recombinant adenovirus expressing M2 Mice IM 2 immunizations (50 μg each) led to the enhanced antibody response. Challenge with LD50 of A/PR/8/34 (H1N1) and 10 LD50 of A/FM/1/47-MA (H1N1) and LD50 A/Thailand/SP-83/2004 (H5N1) showed the significant cross-protection of the vaccine. The important protective role of CD4 + and CD8 + cells was also shown. [119]
T7 bacteriophage nanoparticles Mice SC+ 3 immunizations (109 PFU each) led to the formation of IgG1 and IgG2a M2e-antibodies, as well as a T-cell response. Challenge with 4 LD50 of A/PR/8/34 (H1N1) and X47 showed a high degree of protection. [38]
Rotavirus fragment NSP498–135 Mice SC+ 3 immunizations (10 μg each) with a chimeric protein resulted in the formation of an increased level of antibodies compared with immunization with M2e peptides. The formation of IgG1 M2e antibodies and to a lesser extent IgG2a was induced. Challenge using 3 LD50 of A/PR/8/34 (H1N1) or A/equine/London/72 (H7N7) did not reveal significant differences between the chimeric and peptide vaccine, however lung virus titers 3 d.p.i. were significantly lower in the M2e-NSP4 group. [3]
Keyhole limpet hemocyanin (KLH) or Neisseria meningitides outer membrane protein complex (OMPC) Mice SC or IM+ 3 immunizations (20 μg each) at 4-week intervals led to the formation of high levels of antibodies with cross-reactivity. Challenge with LD90 of A/Hong Kong/68xPR8 reassortant resulted in complete survival and lower weight loss in vaccinated mice compared with controls. [28]
Ferrets IM+ 3 immunizations (100 μg each) at 4-week intervals showed that the OMPC-based vaccine was more immunogenic than the KHL-based vaccine. Challenge with 100 TCID50 A/PR/8/34 (H1N1) revealed significantly lower replication of the challenge virus in the nasal turbinates and lungs.
Rhesus monkeys IM+ 3 immunizations (10 μg each) during 25 weeks (immunization on 0, 8, and 25 weeks) with an OMPC-based vaccine led to the formation of an increased level of M2e antibodies. Sera were examined after challenge with A/Hong Kong/68xPR8 after passive transfer immunization of mice, and protective efficacy was shown.
Brucella abortus lumazine synthase protein (BLS) Mice SC, SC+, IM, IM+, IN, IN+ 3 immunizations (10 μg each) using various routes at 3-week intervals led to the formation of IgG1 and IgG2a M2e-antibodies in different ratios. SC+ immunization produced the highest level of antibodies and was chosen for further study. Challenge with 5 LD50 of A/PR/8/34 (H1N1) showed the protective efficacy of the vaccine. [2]
Malva mosaic virus nanoparticles Mice SC+ 2 immunizations (20 μg each) at a 2-week interval led to the formation of IgG1 and IgG2a M2e-antibodies, whereas immunization with M2e peptides was not immunogenic. Significantly lower replication of the challenge virus in nasal turbinates and lungs was shown after challenge with A/WSN/1933 (H1N1). [70]
Dogs IM+ 3 immunizations (80 μg each) at 3-week intervals led to the formation of cross-reactive M2e-antibodies and revealed the need for adjuvant. Challenge was not performed.
H1N1 HA DNA Mice IM+ 2 immunizations (0.2 μg each) at a 3-week interval led to the formation of cross-reactive M2e-antibodies. High protection of immunized mice was shown against challenge with 5 LD50 of A/Aquatic Bird/Korea/W81/2005. In addition, HA-specific CD8+ and M2e-specific T cell responses were elicited [92]
Salmonella typhimurium flagellin Mice SC 3 immunizations (6 μg each) at 3-week intervals led to the formation of a high level of M2e-antibodies. Full protection of vaccinated mice was shown against challenge with 10 LD50 of A/Aichi/2/68 (H3N2). [113]
Mice SC or IN 2 immunizations (3 μg each) at a 2-week interval led to the formation of a higher rate of M2e-antibodies than immunization with M2e-peptides. There was no decline in the following 10 months. High protection of immunized mice was shown against challenge with LD90 of A/PR/8/34 (H1N1). [46]
Rabbits IM 2 immunizations (15 μg each) at a 3-week interval led to the formation of M2e-antibodies.
Multiple antigenic peptide Mice SC+ Single immunization led to the formation of high levels of M2e antibodies, which insignificantly declined in the following 6 months. 2 immunizations led to significant clearance of virus 3 days after challenge with 10 LD50 A/Beijing/501/09 and protected against weight loss. [141]
DNA expressing fusion M2e-NP protein Pigs SC+ 3 immunizations (200 μg each) at 3-week intervals did not protect animals after challenge with 108 TCID50 of A/Sw/Best/96 (H1N1) but led to more serious signs of disease compared with the control group. [41]
Lipopeptides Mice SC 2 immunizations (20 nmol each) at a 2-week interval with shortened form of M2e (a.a. 2–16) led to the same level of M2e antibody production as immunization with full-length M2e (a.a. 2–24), and led to lower viral titers in lungs and nasal turbinates after challenge with 104.5 PFU of A/Memphis/1/71xA/Bellamy/42 (H3N1) virus. [94]
Keyhole limpet haemocyanin (KLH with full length M2e (M2e-KLH) and M2e2–10 (SP1-KHL) Mice IP+ 3 immunizations at 3-week intervals led to the formation of M2e-antibodies for both vaccines. Vaccinated groups were more protected than the control group against challenge with 4 LD50 of A/PR/8/34 (H1N1). M2e-KLH was more immunogenic and protective than SP1-KHL. [18]
Rabbits n/m 3 immunizations at 3-week intervals showed greater immunogenicity of SP1-KHL. Serum from immunized rabbits provided protection in a mice passive transfer study against challenge with 4 LD50 of A/PR/8/34 (H1N1). SP1-KHL was also more immunogenic in outbred New Zealand white rabbits than in inbred BALB/c mice.
VLP Mice IM 2 immunizations at a 4-week interval led to the formation of M2e-antibodies, and protected mice against challenge with 4 LD50 of A/Philippines/2/82(H3N2) 4 weeks and 8 months after boost. [58]
M13 phage SPF chickens IM+ (1st), IM (2nd) 2 immunizations with the hybrid phage expressing shortened form of M2e (a.a. 2–9) at a dose of 1 × 1010 phage/200 μL produced specific antibodies against M2e (2–9) in broiler chickens. [80]
CTA1-DD Mice IN 2 immunizations at 3-week intervals induced strong M2e-specific serum antibody response and stimulated significant anti-M2e IgA antibody titers in bronchial lavage. Vaccination provided strong protective immunity against challenge with 4 LD50 of X47 virus. [25]
8C6 and 1B12 antibodies (recognize M2e6–13) Mice IP (passive transfer) Passive transfer with 8C6 and 1B12 led to the formation of a high level of M2e antibodies and 75% protection of vaccinated mice against challenge with 5 LD50 of A/PR/8/34 (H1N1), compared with 0% protection in control group. [78]
M2e-specific IgG2a MAb65 Mice IP (passive transfer) Passive immunization reduced transmission of A/Udorn/72 (H3N2) and A/Hong Kong/68 (H3N2) challenge viruses and led to lower viral titer in lungs and nasal turbinates. [60]
  1. * IP, intraperitoneal: IN, intranasal; SC, subcutaneous; IM, intramuscular; n/m, not mentioned; +, with adjuvant