• Additional Evidence on Serological Correlates of Protection against Measles: An Observational Cohort Study among Once Vaccinated Children Exposed to Measles.

      Woudenberg, Tom; van Binnendijk, Rob; Veldhuijzen, Irene; Woonink, Frits; Ruijs, Helma; van der Klis, Fiona; Kerkhof, Jeroen; de Melker, Hester; de Swart, Rik; Hahné, Susan (2019-10-22)
    • Antibody responses to Bordetella pertussis and other childhood vaccines in infants born to mothers who received pertussis vaccine in pregnancy - a prospective, observational cohort study from the United Kingdom.

      Rice, T F; Diavatopoulos, D A; Smits, G P; van Gageldonk, P G M; Berbers, G A M; van der Klis, F R; Vamvakas, G; Donaldson, B; Bouqueau, M; Holder, B; et al. (2019-02-13)
      The maternal Tdap (tetanus, diphtheria and acellular pertussis) vaccination programme in the United Kingdom has successfully reduced cases of pertussis in young infants. In addition to prevention of pertussis cases, it is also important to investigate the persistence of maternal antibodies during infancy and the possible interference of maternal antibodies with infant responses to vaccines. We recruited mother-infant pairs from vaccinated and unvaccinated pregnancies and measured concentrations of immunoglobulin (Ig)G against pertussis toxin (PTx), filamentous haemagglutinin (FHA), pertactin (Prn), diphtheria toxin (DTx), tetanus toxoid (TTx) Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae in mothers and infants at birth, and in infants at 7 weeks and at 5 months. Thirty-one mother-infant pairs were tested. Tdap-vaccinated women had significantly higher antibody against Tdap antigens, compared to unvaccinated women (DTx, P = 0·01; PTx, FHA, Prn and TTx, P < 0·001). All antibodies were actively transferred to the infants (transfer ratio  > 1) with higher transfer of DTx (P = 0·04) and TTx (P = 0·02) antibody in Tdap-vaccinated pregnancies compared to unvaccinated pregnancies. Infants from Tdap-vaccinated pregnancies had significantly elevated antibodies to all antigens at birth (P < 0.001) and at 7 weeks (FHA, Prn, TTx, P < 0·001; DTx, P = 0.01; PTx, P = 0·004) compared to infants from unvaccinated pregnancies. Infants from Tdap-vaccinated and -unvaccinated pregnancies had comparable antibody concentrations following primary pertussis immunization (PTx, P = 0·77; FHA, P = 0·58; Prn, P = 0·60; DTx, P = 0·09; TTx, P = 0·88). These results support maternal immunization as a method of protecting vulnerable infants during their first weeks of life.
    • Antibody Specificity Following a Recent Infection in Adolescence Is Correlated With the Pertussis Vaccine Received in Childhood.

      Raeven, René H M; van der Maas, Larissa; Pennings, Jeroen L A; Fuursted, Kurt; Jørgensen, Charlotte Sværke; van Riet, Elly; Metz, Bernard; Kersten, Gideon F A; Dalby, Tine (2019-01-01)
      Bordetella (B.) pertussis resurgence affects not only the unvaccinated, but also the vaccinated population. Different vaccines are available, however, it is currently unknown whether the type of childhood vaccination has an influence on antibody responses following a B. pertussis infection later in life. Therefore, the study aim was to profile serum antibody responses in young adults with suspected B. pertussis infections, immunized during childhood with either whole-cell (wPV) or monocomponent acellular pertussis (aPV) vaccines. Serum anti-pertussis toxin (PTx) IgG antibody levels served as an indicator for a recent B. pertussis infection. Leftover sera from a diagnostic laboratory from 36 Danish individuals were included and divided into four groups based on immunization background (aPV vs. wPV) and serum anti-PTx IgG levels (- vs. +). Pertussis-specific IgG/IgA antibody levels and antigen specificity were determined by using multiplex immunoassays (MIA), one- and two-dimensional immunoblotting (1 & 2DEWB), and mass spectrometry. Besides enhanced anti-PTx levels, wPV(+) and aPV(+) groups showed increased IgG and IgA levels against pertactin, filamentous hemagglutinin, fimbriae 2/3, and pertussis outer membrane vesicles (OMV). In the wPV(-) and aPV(-) groups, only low levels of anti-OMV antibodies were detected. 1DEWB demonstrated that antibody patterns differed between groups but also between individuals with the same immunization background and anti-PTx levels. 2DWB analysis for serum IgG revealed 133 immunogenic antigens of which 40 were significantly different between groups allowing to differentiate wPV(+) and aPV(+) groups. Similarly, for serum IgA, 7 of 47 immunogenic protein spots were significantly different. This study demonstrated that B. pertussis infection-induced antibody responses were distinct on antigen level between individuals with either wPV or aPV immunization background. Importantly, only 2DEWB and not MIA could detect these differences indicating the potential of this method. Moreover, in individuals immunized with an aPV containing only PTx in childhood, the infection-induced antibody responses were not limited to PTx alone.
    • Assessment of herd effects among women and heterosexual men after girls-only HPV16/18 vaccination in the Netherlands: A repeated cross-sectional study.

      Woestenberg, Petra J; Bogaards, Johannes A; King, Audrey J; Leussink, Suzan; van der Sande, Marianne Ab; Hoebe, Christian Jpa; van Benthem, Birgit Hb (2018-11-13)
      Data on the impact of human papillomavirus (HPV) vaccination on the population HPV prevalence are largely obtained from women. We assessed the impact of the girls-only HPV16/18 vaccination program in the Netherlands that started in 2009, on trends in HPV prevalence among women and heterosexual men, using data from the PASSYON study. In this cross-sectional study, the HPV prevalence among 16- to 24-year-old visitors to sexually transmitted infection clinics was assessed in 2009, 2011, 2013, and 2015. We compared the genital postvaccination HPV prevalence with the prevaccination prevalence (2009) using Poisson GEE models. In total, we included 4,996 women and 1,901 heterosexual men. The percentage of women who reported to be vaccinated increased from 2.3% in 2009 to 37% in 2015. Among all women, the HPV16/18 prevalence decreased from 23% prevaccination to 15% in 2015 (adjusted prevalence ratio [aPR] 0.62, p
    • Capturing multiple-type interactions into practical predictors of type replacement following human papillomavirus vaccination.

      Man, Irene; Auranen, Kari; Wallinga, Jacco; Bogaards, Johannes A (2019-05-27)
      Current HPV vaccines target a subset of the oncogenic human papillomavirus (HPV) types. If HPV types compete during infection, vaccination may trigger replacement by the non-targeted types. Existing approaches to assess the risk of type replacement have focused on detecting competitive interactions between pairs of vaccine and non-vaccine types. However, methods to translate any inferred pairwise interactions into predictors of replacement have been lacking. In this paper, we develop practical predictors of type replacement in a multi-type setting, readily estimable from pre-vaccination longitudinal or cross-sectional prevalence data. The predictors we propose for replacement by individual non-targeted types take the form of weighted cross-hazard ratios of acquisition versus clearance, or aggregate odds ratios of coinfection with the vaccine types. We elucidate how the hazard-based predictors incorporate potentially heterogeneous direct and indirect type interactions by appropriately weighting type-specific hazards and show when they are equivalent to the odds-based predictors. Additionally, pooling type-specific predictors proves to be useful for predicting increase in the overall non-vaccine-type prevalence. Using simulations, we demonstrate good performance of the predictors under different interaction structures. We discuss potential applications and limitations of the proposed methodology in predicting type replacement, as compared to existing approaches. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.
    • Incidence and Risk Factors for Invasive Pneumococcal Disease and Community-acquired Pneumonia in Human Immunodeficiency Virus-Infected Individuals in a High-income Setting.

      Garcia Garrido, Hannah M; Mak, Anne M R; Wit, Ferdinand W N M; Wong, Gino W M; Knol, Mirjam J; Vollaard, Albert; Tanck, Michael W T; Van Der Ende, Arie; Grobusch, Martin P; Goorhuis, Abraham (2019-10-21)
    • Occurrence of human papillomavirus (HPV) type replacement by sexual risk-taking behaviour group: Post-hoc analysis of a community randomized clinical trial up to nine years after vaccination (IV).

      Gray, Penelope; Luostarinen, Tapio; Vänskä, Simopekka; Eriksson, Tiina; Lagheden, Camilla; Man, Irene; Palmroth, Johanna; Pimenoff, Ville N; Söderlund-Strand, Anna; Dillner, Joakim; et al. (2019-02-05)
      Oncogenic non-vaccine human papillomavirus (HPV) types may conceivably fill the vacated ecological niche of the vaccine types. The likelihood of this may differ by the risk of acquiring HPV infections. We examined occurrence of HPV types among vaccinated and unvaccinated subgroups of 1992-1994 birth cohorts with differing acquisition risks up to 9 years post-implementation of HPV vaccination in 33 Finnish communities randomized to: Arm A (gender-neutral HPV16/18 vaccination), Arm B (girls-only HPV16/18 vaccination and hepatitis B-virus (HBV) vaccination of boys), and Arm C (gender-neutral HBV vaccination). Out of 1992-94 born resident boys (31,117) and girls (30,139), 8,618 boys and 15,615 girls were vaccinated respectively with 20-30% and 50% coverage in 2007-09. In 2010-13, 8,868 HPV16/18 and non-HPV vaccinated females, and in 2014-16, 5,574 originally or later (2010-13) HPV16/18 vaccinated females attended two cervical sampling visits, aged 18.5 and 22-years. The samples were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68 using PCR followed by MALDI-TOF MS. HPV prevalence ratios (PR) between Arms A/B vs C were calculated for Chlamydia trachomatis positives (core-group), and negatives (general population minus core group). At both visits the vaccine-protected HPV type PRs did not significantly differ between the core-group and non-core group. Among the vaccinated 18-year-olds, HPV51 occurrence was overall somewhat increased (PR