Table 4.
Experimental adjuvants assist influenza vaccines to induce cross-protective immunity.
| Adjuvant | Vaccine and Immunization Regimen | Study Subjects | Cross-Protective Immunity | Safety | Reference |
|---|---|---|---|---|---|
| SWE | Split virion vaccine of A/Shanghai/2/2013 (H7N9)-A/Puerto Rico/8/34 (PR8)-IDCDC-RG32A.3; two doses (21 days apart); IM | Ferrets | HI titer against heterologous Eurasian and North American Lineages of H7N2, H7N3, H7N7, and H7N9 viruses, Heterologous protection against A/Anhui/1/2013 (H7N9) virus | Not studied | [116] |
| AddaVax | Inactivated whole virus vaccine of reassortant A/Hong Kong/125/2017 (H7N9) and PR8 backbone; two doses (28 days apart); IM | Ferrets | HI titer and protection against highly pathogenic heterologous H7N9 rGD/3-NA294R virus | Not studied | [117] |
| GLA-SE | Plant-produced H5-VLP (A/Indonesia/05/2005, clade 2); two doses (21 days apart); IM | Non-elderly adults | Polyfunctional and sustained heterologous CD4+ T cell responses against influenza H2 protein | Higher incidences of solicited symptoms and mostly mild or moderate | [134] |
| GLA-AF | Plant-produced H5-VLP (A/Indonesia/05/2005, clade 2); two doses (21 days apart); ID | Non-elderly adults | HI GMI and seroconversion against heterologous clade 2 virus A/Anhui/1/2005 and HI GMI and seroconversion against clade 1 virus A/Vietnam/1203/2004 | Transient erythema; no serious adverse events related to vaccination | [135] |
| GLA-AF | Plant-produced H5-VLP (A/Indonesia/5/05, clade 2); two doses (21 days apart) in mice and guinea pigs; one dose in ferrets; IM or ID | Mice, guinea pig, and ferrets | HI titer and protection against heterologous virus A/Duck/Hunan/795/2002 in mice and protection against clade 1 strain A/Vietnam/1203/04 in ferrets | Guinea pigs: no temperature spikes or body weight decrease; Ferrets: no local reactions or body temperature increase | [135] |
| GLA-AF | Recombinant HA (rHA) of H5N1 A/Vietnam/1203/04 or A/Indonesia /05/05 viruses; one dose in mice and one or two doses (21 days apart) in ferrets; IM | Mice and ferrets | Cross-clade HI titer and protection | Not studies | [136] |
| MPL and CPG combination | Split virion vaccine of A/California/04/2009 H1N1; one or two doses (21 days apart); IM | Mice | HI titer and protection against heterosubtypic reassortant H5N1 A/Vietnam/1203/2004 virus | Not studied | [137] |
| TLR4 and TLR7 agonist combination | rHA of PR8 H1N1; chimeric rHA (same stalk region); one dose (rHA) or 3 doses (chimeric rHA); IM | Mice | Heterologous protection against A/California/04/2009 H1N1 virus; Heterologous protection against B/Florida/04/2006 (Yamagata lineage); Heterosubtypic protection against reassortant A/Vietnam/1203/2004 H5N1 virus | Not studied | [138] |
| Imiquimod (Aldara) | TIV (Intanza); one dose; ID | Healthy student volunteers | Heterologous HI and MN titer against non-vaccine strains | More common redness and swelling; no serious adverse events related to vaccination | [139] |
| 3M-052 | rHA of A/Vietnam/1203/04 H5N1; two doses with 28 days apart in mice; one dose in ferrets; IM | Mice and ferrets | Cross-clade antibody binding in mice and heterologous protection against A/Whooper Swan/Mongolia/ 244/05 H5N1 virus in ferrets | Not studied | [140] |
| Membrane-anchored flagellin | HA/M1VLPs based on PR8 virus; two doses (28 days apart); IM or IN | Mice | Heterosubtypic protection against A/Philippines/82 (H3N2) virus | Not studied | [141,142] |
| ISCOMs | Fluzone® monovalent subunit vaccine of A/Taiwan/1/86 H1N1; two doses (21 days apart); subcutaneous | Mice | Heterosubtypic protection against A/Japan/305/57 (H2N2) virus due to CTL but not antibody responses | Not studied | [143] |
| Matrix-M | Trivalent virosomal vaccine; one to three doses (21 days apart); IM | Mice | Heterologous protection against influenza A and B strains | Not studied | [144] |
| Matrix-M | TIV; two doses (21 days apart); IM | Mice and ferrets | Heterologous protection against H3N2 strain A/Texas/71/2007; Heterosubtypic protection against H5N1 and H7N7 viruses | Not studied | [145,146] |
| Matrix-M | Inactivated virosomal H5N1 vaccine of A/Vietnam/1194/2004 (clade 1); two doses (21 days apart); IM | Non-elderly adults | HI titer against heterologous clade 1 virus (A/Cambodia/R0405050/2007) and cross-clade HI titer against clade 2 viruses (A/Indonesia/5/2005 and A/turkey/Turkey/1/2005) | Not studied | [147] |
| Cholera toxin | Inactivated PR8 vaccine; two doses (14 days apart); IN | Mice | Heterologous protection against H1N1 and heterosubtypic protection against H3N2 virus (A/Philippines/82) | Not studied | [148] |
| Cholera toxin B subunit | HA of A/Fukuoka /C29/85 (H3N2) or A/Sichuan/2/87 (H3N2); one dose; IN | Mice | Heterologous protection against H3N2 virus (A/Guizhou/54/89-X) | Not studied | [149] |
| LT (R192G) | Whole-inactivated X-31 (H3N2) vaccine; three doses (7 days apart); IN | Mice | Heterosubtypic protection against H5N1 virus | Not studied | [150] |
| CAF01 | TIV; two doses (3-4 weeks apart); subcutaneous | Mice and ferrets | Heterologous protection against H1N1 viruses | Not studied | [151,152] |
| NAFL | Inactivated PR8 vaccine; one dose; transdermal | Mice and miniature pigs | Heterologous and heterosubtypic protection against H1N1 and H3N2 viruses in mice | Minimal local reactions in miniature pigs | [153] |