Journal
HUMAN VACCINES & IMMUNOTHERAPEUTICS
Volume 11, Issue 5, Pages 1209-1222Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/21645515.2015.1016674
Keywords
adenovirus vector; broadly neutralizing antibodies; cellular immunity; hemagglutinin; humoral immunity; influenza; mucosal immunity; universal vaccine; flu, influenza; IFV, Influenza virus; HA, hemagglutinin; NA, neuraminidase; NP, nucleoprotein; M1, matrix protein 1; M2, matrix protein 2; IIVV, inactivated influenza virus vaccine; LAIV, live attenuated influenza vaccine; Ad: adenovirus; rAd, recombinant adenovirus; ITRs, inverted terminal repeats; HDAd, helper-dependent adenoviral; HEK293, human embryonic kidney 293 cell; RCA, replication competent adenovirus; DVD, drug-vaccine duo; HI, hemagglutination inhibition; mAbs, monoclonal antibodies; Fc gamma Rs, Fc receptors for IgG; ADCC, antibody-dependent cell-mediated cytotoxicity; IF-gamma, interferon-gamma; IL-2, interleukin-2; MHC-I, major histocompatibility complex class I; HLA, human leukocyte antigen; VAERD, vaccine-associated enhanced respiratory disease; CTLs, cytotoxic T lymphocytes; APC, antigen-presenting cell; DC, lung dendritic cells; CAR, Coxsackie-Adenovirus Receptor
Categories
Funding
- Department of Science and Technology of Yunnan Province [2012AE001]
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Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8(+) T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides 'self-adjuvanting' activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches.
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