Glycoconjugate vaccines and immune interference: A review

The Pediatric Infectious Disease Unit, The Faculty of Health Sciences, Ben Gurion University of the Negev and Soroka University Medical Center, Beer-Sheva, Israel.
Vaccine (Impact Factor: 3.62). 08/2010; 28(34):5513-23. DOI: 10.1016/j.vaccine.2010.06.026
Source: PubMed


Bacterial polysaccharide-protein conjugate vaccines (Haemophilus influenzae type b [Hib], pneumococcal and meningococcal conjugates) have revolutionized pediatric vaccination strategies. The widely used carrier proteins are tetanus toxoid (TT), diphtheria toxoid (DT) and diphtheria toxoid variant CRM197 protein, DT conjugates being in general less immunogenic. Multivalent conjugates using TT were found to be at risk for reduced polysaccharide responses, whilst multivalent CRM197 conjugates are at lower risk for this, but may be at higher risk of inducing bystander interference, particularly affecting Hib and hepatitis B immune responses. Novel carriers avoiding these issues could enable the further development of pediatric schedules and combinations.

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    • "In addition, several randomised controlled trials (RCTs) have reported greater Hib antibody interference with increasing amount of CRM administered [3] [4] [5]. In the UK, the 7-valent pneumococcal conjugate vaccine (PCV7; Prevenar ® ; Pfizer Ltd., Kent, UK) was replaced with a newly licensed 13-valent conjugate vaccine (PCV13; Prevenar13 ® ; Pfizer Ltd., Kent, UK), from April 2010. "
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    ABSTRACT: An open, non-randomised study was undertaken in England during 2011-12 to evaluate vaccine antibody responses in infants after completion of the routine primary infant immunisation schedule, which included two doses of meningococcal group C (MenC) conjugate (MCC) vaccine at 3 and 4 months. Any of the three licensed MCC vaccines could be used for either dose, depending on local availability. Healthy term infants registered at participating general practices (GPs) in Hertfordshire and Gloucestershire, UK, were recruited prospectively to provide a single blood sample four weeks after primary immunisation, which was administered by the GP surgery. Vaccination history was obtained at blood sampling. MenC serum bactericidal antibody (SBA) and IgG antibodies against Haemophilus influenzae b (Hib), pertussis toxin (PT), diphtheria toxoid (DT), tetanus toxoid (TT) and thirteen pneumococcal serotypes were analysed according to MCC vaccines received. MenC SBA responses differed significantly (P<0.001) according to MCC vaccine schedule as follows: MenC SBA geometric mean titres (GMTs) were significantly lower in infants receiving a diphtheria cross-reacting material-conjugated MCC (MCC-CRM) vaccine followed by TT-conjugated MCC (MCC-TT) vaccine (82.0; 95% CI, 39-173; n=14) compared to those receiving two MCC-CRM (418; 95% CI, 325-537; n=82), two MCC-TT (277; 95% CI, 223-344; n=79) or MCC-TT followed by MCC-CRM (553; 95% CI, 322-949; n=18). The same group also had the lowest Hib geometric mean concentrations (0.60μg/mL, 0.27-1.34) compared to 1.85μg/mL (1.23-2.78), 2.86μg/mL (2.02-4.05) and 4.26μg/mL (1.94-9.36), respectively. Our results indicate that MCC vaccines with different carrier proteins are not interchangeable. When several MCC vaccines are available, children requiring more than one dose should receive MCC vaccines with the same carrier protein or, alternatively, receive MCC-TT first wherever possible. Copyright © 2014. Published by Elsevier Ltd.
    Vaccine 12/2014; 33(5). DOI:10.1016/j.vaccine.2014.12.018 · 3.62 Impact Factor
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    • "This is supported by the observation that rSBA responses were 1.9- to 4-fold higher in individuals who mounted a booster response to TT (concentrations ≥1.0 IU/ml after vaccination) compared with those in whom the magnitude of the post-vaccination anti-TT concentration was lower. Immunogenicity of conjugate vaccines using DT and CRM197 carrier proteins is known to need prior DT priming to generate optimal responses [40]. Our results support the immunogenicity of MenACWY-TT in TT-unprimed individuals, but suggest that effective TT-priming may be critical to enhance the immune response to subsequent TT conjugate vaccines. "
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    ABSTRACT: BACKGROUND: The burden of invasive meningococcal disease is substantial in older adults in whom the case fatality rate is high. Travelers to regions with high rates of meningococcal disease, such as Hajj pilgrims, are at increased risk of meningococcal infection, and disease transmission from travelers to their close contacts has been documented. In younger individuals, meningococcal conjugate vaccines offer advantages over polysaccharide vaccines in terms of duration of protection and boostability, and induction of herd immune effects through reductions in nasopharyngeal carriage of meningococci. To date, few data are available evaluating meningococcal conjugate vaccine use in adults >55 years of age. OBJECTIVE: To evaluate the immunogenicity and safety of quadrivalent meningococcal serogroups A, C, W-135 and Y vaccine with all serogroups conjugated to tetanus toxoid (MenACWY-TT, Nimenrix™, GlaxoSmithKline, Belgium) and a licensed quadrivalent polysaccharide vaccine (MenPS, Mencevax™ GlaxoSmithKline, Belgium) in adults >55 years of age. METHODS: This was a phase IIIb, open-label, randomized (3:1), controlled study conducted at one study center in Lebanon. A total of 400 healthy adults between 56 and 103 years of age without previous MenPS or tetanus toxoid vaccination within the previous 5 years or meningococcal conjugate vaccination at any time previously were included. They received a single-dose vaccination with MenACWY-TT or MenPS with blood sampling before and 1 month after vaccination. The main outcome measures were serum bactericidal activity (rabbit complement source: rSBA) vaccine response (VR) rate [rSBA titer of ≥1:32 in initially seronegative subjects (rSBA titer <1:8); ≥4-fold increase in subjects with pre-vaccination rSBA titers between 1:8 and 1:128, and ≥2-fold increase in subjects with pre-vaccination rSBA titers ≥1:128]. The percentages of subjects with rSBA titers ≥1:8 and ≥1:128 and rSBA geometric mean titers (GMTs) were assessed. Solicited adverse events were recorded for 4 days following vaccination, and all other adverse events, including the incidence of new onset chronic diseases, were recorded for 31 days after vaccination. RESULTS: One month after a single dose of MenACWY-TT, the rSBA VR rate in the MenACWY-TT group was 76.6 % for serogroup A, 80.3 % for serogroup C, 77.5 % for serogroup W-135 and 81.9 % for serogroup Y. VR rates in the MenPS group were 91.7, 84.8, 87.1 and 89.1 %, respectively. One month after vaccination, ≥93.2 % of subjects in the MenACWY-TT group and ≥93.9 % in the MenPS group had rSBA titers ≥1:128. In each group, GMTs increased by ≥13-fold for each serogroup. rSBA VR and GMTs tended to be lower in subjects who were over 65 years compared to 56-65 years of age. Only 6.3 % of MenACWY-TT recipients had anti-TT ≥0.1 IU/ml prior to vaccination, increasing to 28.1 % post-vaccination. The rSBA GMTs were 1.9- to 4-fold higher in anti-TT responders. Each local and general solicited symptom was reported by no more than 3.0 % of subjects in either group. No serious adverse events were considered vaccine related. CONCLUSION: In adults 56 years of age and older, MenACWY-TT was immunogenic, with a vaccine response rate ≥76 % and with ≥93 % of subjects achieving rSBA titers ≥1:128 against all four serogroups after a single dose. MenACWY-TT induced low anti-TT concentrations in this population, which deserves further study.
    Drugs & Aging 03/2013; 30(5). DOI:10.1007/s40266-013-0065-0 · 2.84 Impact Factor
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    • "Additionally, the carrier protein needs to be carefully chosen. In commercially available conjugated vaccines, the carrier proteins are often inactivated bacterial toxins from Clostridium tetani and Corynebacterium diphtheria, which were chosen for their ability to induce an immune response (Dagan et al., 2010). Despite being highly immunogenic, none of the currently used toxins are substrates for PglB because they do not contain the glycosylation consensus sequon. "
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    ABSTRACT: The discovery of the Campylobacter jejuni N-linked glycosylation system combined with its functional expression in Escherichia coli marked the dawn of a new era in glycoengineering. The process, termed protein glycan coupling technology (PGCT), has, in particular, been applied to the development of glycoconjugate vaccines. In this review, we highlight recent technical developments in this area, including the first structural determination of the coupling enzyme PglB, the use of glycotags for optimal glycan attachment and the possible applications of other glycosylation systems and how these may improve and extend PGCT.
    Journal of Medical Microbiology 04/2012; 61(Pt 7):919-26. DOI:10.1099/jmm.0.039438-0 · 2.25 Impact Factor
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