Activation of cross-reactive mucosal T and B cell responses in human nasopharynx-associated lymphoid tissue in vitro by Modified Vaccinia Ankara-vectored influenza vaccines

作者：Mullin Jennifer; Ahmed Muhammed S; Sharma Ravi; Upile Navdeep; Beer Helen; Achar Priya; Puksuriwong Suttida; Ferrara Francesca; Temperton Nigel; McNamara Paul; Lambe Teresa; Gilbert Sarah C; Zhang Qibo

来源：Vaccine, 2016, 34(14): 1688-1695.

DOI：10.1016/j.vaccine.2016.02.028

• Mucosal immunity
• Influenza vaccine
• Antibody response
• Nasopharynx-associated lymphoid-tissue (NALT)
• MVA-vectored vaccine
• Children and adults

Recent efforts have been focused on the development of vaccines that could induce broad immunity against influenza virus, either through T cell responses to conserved internal antigens or B cell response to cross-reactive haemagglutinin (HA). We studied the capacity of Modified Vaccinia Ankara (MVA)-vectored influenza vaccines to induce cross-reactive immunity to influenza virus in human nasopharynx-associated lymphoid tissue (NALT) in vitro. Adenotonsillar cells were isolated and stimulated with MVA vaccines expressing either conserved nucleoprotein (NP) and matrix protein 1 (M1) (MVA-NP-M1) or pandemic H1N1 HA (MVA-pdmH1HA). The MVA vaccine uptake and expression, and T and B cell responses were analyzed. MVA-vectored vaccines were highly efficient infecting NALT and vaccine antigens were highly expressed by B cells. MVA-NP-MI elicited T cell response with greater numbers of IFN gamma-producing D4+ T cells and tissue-resident memory T cells than controls. MVA-pdmH1HA induced cross-reactive anti-HA antibodies to a number of influenza subtypes, in an age-dependent manner. The cross-reactive antibodies include anti-avian H5N1 and mainly target HA2 domain. Conclusion: MVA vaccines are efficient in infecting NALT and the vaccine antigen is highly expressed by B cells. MVA vaccines expressing conserved influenza antigens induce cross-reactive T and B cell responses in human NALT in vitro, suggesting the potential as mucosal vaccines for broader immunity against influenza.

• 出版日期2016-3-29