Some extensions in continuous models for immunological correlates of protection

Detail of results of case-cohort investigation. (DOCX 41 kb

A Dose-Response Study of a Live Attenuated Varicella-Zoster Virus (Oka Strain) Vaccine Administered to Adults 55 Years of Age and Older

Decreased cell-mediated immune (CMI) response to varicella-zoster virus (VZV) is correlated with an increased risk of reactivation of latent virus from dorsal root sites, leading to herpes zoster. The cell-mediated and humoral immunogenicity of three concentrations (3200, 8500, and 41,650 pfu/dose) of a live attenuated VZV vaccine (Oka strain; VZV/Oka) was compared with a control pneumococcal polysaccharide vaccine in 200 healthy adults who were ≥55 years old. Six weeks after vaccination, the VZV-specific CMI response (as measured by stimulation index values and precursor cell frequencies) was enhanced in all VZV/Oka vaccine groups compared with the control group (for all VZV/Oka groups combined vs. controls, tested with VZV crude antigen: stimulation index, P < .001; precursor cell frequency, P < .001). Geometric mean titers of anti-VZV antibodies increased in all VZV/Oka vaccine groups but remained unchanged in the control vaccine group. No dose effect of VZV/Oka vaccine was observed for CMI or humoral response

Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model

<p>Abstract</p> <p>Background</p> <p>Antibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI) assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy.</p> <p>Methods</p> <p>We present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information.</p> <p>Results</p> <p>A significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B) and the vaccination status of the individuals.</p> <p>Conclusion</p> <p>Although limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile.</p

Modeling the long-term persistence of neutralizing antibody in children and toddlers after vaccination with live attenuated Japanese encephalitis chimeric virus vaccine

The live-attenuated Japanese encephalitis chimeric virus vaccine JE-CV (IMOJEV®, Sanofi Pasteur) elicits a robust antibody response in children, which wanes over time. Clinical efficacy is based on a correlate of protection against JE infection defined as neutralizing antibody levels equal to or greater than the threshold of 10 (1/dil). Information on the duration of persistence of the JE antibody response above this threshold is needed. We constructed statistical models using 5-year persistence data from a randomised clinical trial (NCT00621764) in children (2–5 years old) primed with inactivated JE vaccine who received a booster dose of JE-CV, and in JE-naïve toddlers (12–24 months) who received a JE-CV single dose primary vaccination. Models were constructed using a Bayesian Monte-Carlo Markov Chain approach and implemented with OpenBugs V3.2.1. Antibody persistence was predicted for up to 10 years following JE-CV vaccination. Findings from a piecewise model with 2 phases (children) and a classic linear model (toddlers) are presented. For children, predicted median antibody titers (77 [2.5th–97.5th percentile range 41–144] 1/dil) remained above the threshold for seroprotection over the 10 years following booster JE-CV vaccination; the predicted median duration of protection was 19.5 years. For toddlers, 10 years after JE-CV primary vaccination median antibody titers were predicted to wane to around the level required for seroprotection (10.8 [5.8–20.1] 1/dil). A booster dose of JE-CV in children is predicted to provide long-term protection against JE. Such data are useful to facilitate decisions on implementation of and recommendations for future vaccination strategies

Additional file 3: of Some extensions in continuous models for immunological correlates of protection

Illustrative SAS code to create the datasets reconstructed from published sources and fit models. (DOCX 50 kb

Immune response to octavalent diphtheria- and tetanus-conjugated pneumococcal vaccines is serotype- and carrier-specific: the choice for a mixed carrier vaccine.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Development of protein-conjugated pneumococcal vaccines for infants has led to formulations that are immunogenic in the age group at highest risk for pneumococcal diseases. This study focuses on the search for an optimal formulation. METHODS: In a randomized trial Icelandic infants (n = 160) were immunized at age 3, 4 and 6 months with one of two octavalent pneumococcal conjugate vaccines (serotypes 3, 4, 6B, 9V, 14, 18C, 19F and 23F conjugated to diphtheria toxoid (PncD) or tetanus protein (PncT) followed with a booster of either the same conjugate or 23-valent polysaccharide vaccine at 13 months. Safety data were collected after each vaccination, and IgG responses (enzyme-linked immunosorbent assay) were measured at 3, 4, 6, 7, 13 and 14 months. RESULTS: Both conjugates were safe and caused fewer local reactions than the routine vaccines (P or = 0.15 microg/ml. The PncD gave better primary responses to serotypes 3, 9V and 18C, whereas PncT gave better response to serotype 4. Similar responses were induced to the other serotypes. Good booster IgG responses were obtained in all vaccine groups; 97.5 to 100% of subjects reached > or = 1 microg/ml. CCONCLUSIONS: Both octavalent pneumococcal conjugates were safe and immunogenic in infants. Based on the results from this and similar trials, a mixed diphtheria and tetanus pneumococcal conjugate vaccine was designed to provide the optimal immune response to each serotype

Immune response to octavalent diphtheria- and tetanus-conjugated pneumococcal vaccines is serotype- and carrier-specific: the choice for a mixed carrier vaccine.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Development of protein-conjugated pneumococcal vaccines for infants has led to formulations that are immunogenic in the age group at highest risk for pneumococcal diseases. This study focuses on the search for an optimal formulation. METHODS: In a randomized trial Icelandic infants (n = 160) were immunized at age 3, 4 and 6 months with one of two octavalent pneumococcal conjugate vaccines (serotypes 3, 4, 6B, 9V, 14, 18C, 19F and 23F conjugated to diphtheria toxoid (PncD) or tetanus protein (PncT) followed with a booster of either the same conjugate or 23-valent polysaccharide vaccine at 13 months. Safety data were collected after each vaccination, and IgG responses (enzyme-linked immunosorbent assay) were measured at 3, 4, 6, 7, 13 and 14 months. RESULTS: Both conjugates were safe and caused fewer local reactions than the routine vaccines (P or = 0.15 microg/ml. The PncD gave better primary responses to serotypes 3, 9V and 18C, whereas PncT gave better response to serotype 4. Similar responses were induced to the other serotypes. Good booster IgG responses were obtained in all vaccine groups; 97.5 to 100% of subjects reached > or = 1 microg/ml. CCONCLUSIONS: Both octavalent pneumococcal conjugates were safe and immunogenic in infants. Based on the results from this and similar trials, a mixed diphtheria and tetanus pneumococcal conjugate vaccine was designed to provide the optimal immune response to each serotype