Scherer Erin M, Smith Robin A, Simonich Cassandra A, Niyonzima Nixon, Carter Joseph J, Galloway Denise A
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, Washington, United States of America.
PLoS Pathog. 2014 Oct 16;10(10):e1004461. doi: 10.1371/journal.ppat.1004461. eCollection 2014 Oct.
Licensed human papillomavirus (HPV) vaccines provide near complete protection against the types of HPV that most commonly cause anogenital and oropharyngeal cancers (HPV 16 and 18) when administered to individuals naive to these types. These vaccines, like most other prophylactic vaccines, appear to protect by generating antibodies. However, almost nothing is known about the immunological memory that forms following HPV vaccination, which is required for long-term immunity. Here, we have identified and isolated HPV 16-specific memory B cells from female adolescents and young women who received the quadrivalent HPV vaccine in the absence of pre-existing immunity, using fluorescently conjugated HPV 16 pseudoviruses to label antigen receptors on the surface of memory B cells. Antibodies cloned and expressed from these singly sorted HPV 16-pseudovirus labeled memory B cells were predominantly IgG (>IgA>IgM), utilized diverse variable genes, and potently neutralized HPV 16 pseudoviruses in vitro despite possessing only average levels of somatic mutation. These findings suggest that the quadrivalent HPV vaccine provides an excellent model for studying the development of B cell memory; and, in the context of what is known about memory B cells elicited by influenza vaccination/infection, HIV-1 infection, or tetanus toxoid vaccination, indicates that extensive somatic hypermutation is not required to achieve potent vaccine-specific neutralizing antibody responses.
许可使用的人乳头瘤病毒（HPV）疫苗在接种给对这些类型病毒无预先免疫的个体时，能为最常导致肛门生殖器和口咽癌的HPV类型（HPV 16和18）提供近乎完全的保护。与大多数其他预防性疫苗一样，这些疫苗似乎通过产生抗体来发挥保护作用。然而，对于HPV疫苗接种后形成的免疫记忆（长期免疫所必需），人们几乎一无所知。在此，我们从在无预先免疫情况下接种了四价HPV疫苗的女性青少年和年轻女性中，利用荧光共轭HPV 16假病毒标记记忆B细胞表面的抗原受体，鉴定并分离出了HPV 16特异性记忆B细胞。从这些经单克隆分选的HPV 16假病毒标记的记忆B细胞中克隆并表达的抗体主要为IgG（>IgA>IgM），利用了多种可变基因，并且尽管仅具有平均水平的体细胞突变，但在体外能有效中和HPV 16假病毒。这些发现表明，四价HPV疫苗为研究B细胞记忆的发展提供了一个极佳的模型；并且，结合关于流感疫苗接种/感染、HIV-1感染或破伤风类毒素疫苗接种所引发的记忆B细胞的已知情况，表明实现有效的疫苗特异性中和抗体反应并不需要广泛的体细胞超突变。
