Sato Kayoko, Takahashi Yoshimasa, Adachi Yu, Asanuma Hideki, Ato Manabu, Tashiro Masato, Itamura Shigeyuki
Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan.
Department of Immunology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
Heliyon. 2019 Jan 3;5(1):e01113. doi: 10.1016/j.heliyon.2018.e01113. eCollection 2019 Jan.
The immunogenicities of inactivated whole and split virus vaccines derived from influenza A/H1N1pdm09 virus were compared in a mouse model. We demonstrated the unique properties of whole virus vaccine boosters on the serum memory antibody response in mice. Consistent with previous studies, booster immunization with either whole or split virus vaccines of A/H1N1pdm09 virus produced comparable titers of serum antibodies with hemagglutination inhibition and virus-neutralizing activities. However, superior protection against the challenge infection was unexpectedly observed in mice primed and boosted with whole virus vaccines compared with those treated with split virus vaccines, despite similar levels of antibody titers in each group. Immune serum antibodies were shown to be primarily responsible for this protection via passive transfer experiments of immune serum antibodies to naive recipient mice. Moreover, this protection correlated with elevated affinity maturation of the antibodies. Thus, booster immunization with whole virus vaccines elicited a robust serum antibody response with high avidity to the virus, which was not measurable via conventional serological assays.
在小鼠模型中比较了源自甲型H1N1pdm09流感病毒的灭活全病毒疫苗和裂解病毒疫苗的免疫原性。我们证明了全病毒疫苗加强免疫对小鼠血清记忆抗体反应的独特特性。与先前的研究一致，用甲型H1N1pdm09病毒的全病毒疫苗或裂解病毒疫苗进行加强免疫产生了具有血凝抑制和病毒中和活性的相当滴度的血清抗体。然而，尽管每组抗体滴度水平相似，但与用裂解病毒疫苗处理的小鼠相比，用全病毒疫苗进行初免和加强免疫的小鼠对攻击感染的保护作用出人意料地更强。通过将免疫血清抗体被动转移到未免疫的受体小鼠的实验表明，免疫血清抗体是这种保护作用的主要原因。此外，这种保护作用与抗体亲和力成熟度的提高相关。因此，用全病毒疫苗进行加强免疫引发了对病毒具有高亲和力的强大血清抗体反应，这是通过传统血清学检测无法测量的。
