We are grateful to Dr R Kellner for statistical

advice

We are grateful to Dr. R. Kellner for statistical

advice. The study was part of the Fraunhofer Gesellschaft PROFIL “Mucosal Nano-Vaccine Against Influenza”. “
“Oncogenic strains of the human papillomavirus (HPV) cause cervical cancer [1]; and two particular strains, HPV16 or HPV18, have been identified in over 70% of cervical cancers [2]. The AS04-adjuvanted HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline [GSK] Biologicals SA) is a prophylatic vaccine for the prevention of cervical cancer and contains recombinant virus-like particles (VLPs1) assembled from the L1 major capsid proteins of HPV16 and HPV18. The HPV-16/18 vaccine has demonstrated very high efficacy against persistent infections and high-grade lesions associated with HPV-16/18 as well as cross-protective efficacy against other oncogenic HPV such as HPV31 and 45 [3] and [4]. Overall, the vaccine efficacy against cervical INCB024360 research buy intraepithelial neoplasias

graded 3 or greater in a cohort of HPV DNA-negative women has been estimated at 93.2% (95% CI 78.9–98.7), irrespective of HPV type [3]. Since the preferred age range for HPV-16/18 vaccination (9–14 years) is younger than the age range in which efficacy high throughput screening is typically assessed (beyond 16 years), measurement of the concentration and quality of antibody responses in this population is crucial [5] and [6]. Antibodies are thought to play a role in preventing HPV infection of genital mucosa, even though a correlate of protection has yet to be identified [7] and [8]. Typical methods for assessing antigen-specific antibody responses include ELISAs of cervical secretions as well as serum, pseudovirion-based neutralisation assays, all and measuring the frequencies of memory B cells [9], [10] and [11]. The avidity ELISA is another measure of the antibody response. Increased antibody avidity for antigens reflects the process of affinity maturation of B cells in the germinal centres

that in the presence of follicular helper T cells (TFH) progressively produce antibodies with higher affinity via somatic hypermutation events and develop into B memory cells or plasma cells [12], [13] and [14]. Higher avidities of influenza haemagglutinin (HA1)-specific antibodies have been correlated with higher neutralisation titres after a A(H5N1) influenza vaccination schedule where prime and boost injections were 12–24 weeks apart [15]. Similarly, higher antibody avidities have been associated with higher bactericidal activities in the assessment of Haemophilus influenzae type b vaccines [16] and [17] and Streptococcus pneumoniae type 6B and 23F vaccines [18]. In a recent study of women vaccinated with the HPV-16/18 vaccine, relatively higher levels of HPV16 L1-specific antibodies and avidities were associated with the prevention of HPV31 infection of the cervix [19].

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