Estimating vaccine efficacy from household data observed over time

2004 ◽  
Vol 23 (19) ◽  
pp. 2961-2974 ◽  
Author(s):  
Xiaohong M. Davis ◽  
Michael Haber
Keyword(s):  
Vaccine Efficacy ◽  
Household Data ◽  
Over Time

scholarly journals The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 674
Author(s):  
Maíra Aguiar ◽  
Nico Stollenwerk
Keyword(s):  
Vaccine Efficacy ◽  
Careful Consideration ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Vaccine Trials ◽  
Long Time ◽  
Health Need ◽  
The Impact ◽  
Over Time

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (CYD-TDV—Sanofi Pasteur) and DENVax (TAK 003—Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. Although Dengvaxia resulted in serious adverse events and had to be restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods of 12 and 18 months. Although better measurement over a long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, such as for Dengvaxia, we also noted, after comparing the VE estimations for 12- and 18-month periods, that vaccine efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, and brings up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

scholarly journals RV144 Vaccine Imprinting Constrained HIV-1 Evolution Following Breakthrough Infection

2021 ◽  
Author(s):  
Eric Lewitus ◽  
Eric Sanders-Buell ◽  
Meera Bose ◽  
Anne Marie O’Sullivan ◽  
Kultida Poltavee ◽  
...  
Keyword(s):  
Placebo Group ◽  
Vaccine Efficacy ◽  
Vaccine Group ◽  
Efficacy Trial ◽  
Breakthrough Infection ◽  
Diversifying Selection ◽  
Hiv 1 ◽  
Rv144 Vaccine ◽  
Over Time ◽  
Roll Out

Abstract The scale of the HIV-1 epidemic underscores the need for a vaccine. The multitude of circulating HIV-1 strains together with HIV-1’s high evolvability hint that HIV-1 could adapt to a future vaccine. Here we wanted to investigate the effect of vaccination on the evolution of the virus post-breakthrough infection. We analyzed 2,635 HIV-1 env sequences sampled up to a year post-diagnosis from 110 vaccine and placebo participants who became infected in the RV144 vaccine efficacy trial. We showed that the Env signatures sites that were previously identified to distinguish vaccine and placebo participants were maintained over time. In addition, fewer sites were under diversifying selection in the vaccine group than in the placebo group. These results indicate that HIV-1 would possibly adapt to a vaccine upon its roll out.

scholarly journals Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

2021 ◽  
Vol 17 (12) ◽  
pp. e1010022
Author(s):  
Chris Davis ◽  
Nicola Logan ◽  
Grace Tyson ◽  
Richard Orton ◽  
William T. Harvey ◽  
...  
Keyword(s):  
South African ◽  
Vaccine Efficacy ◽  
Antigenic Drift ◽  
Productive Infection ◽  
Subsequent Reduction ◽  
Fold Reduction ◽  
Antibody Titres ◽  
Efficacy Assessment ◽  
Induced Immunity ◽  
Over Time

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

scholarly journals The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

2020 ◽  
Author(s):  
Maíra Aguiar ◽  
Nico Stollenwerk
Keyword(s):  
Vaccine Efficacy ◽  
Careful Consideration ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Vaccine Trials ◽  
Long Time ◽  
Health Need ◽  
The Impact ◽  
Over Time

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (Sanofi Pasteur) and DENVax (Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. While Dengvaxia resulted in serious adverse events and is restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods. Although better measurement over long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, we also compare the VE estimations for 12 and 18 months and we observe that the efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, bring up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

scholarly journals Approximating instantaneous vaccine efficacy from cumulative vaccine efficacy

2018 ◽  
Author(s):  
Kevin van Zandvoort ◽  
Andrew Clark ◽  
Mark Jit ◽  
Stefan Flasche
Keyword(s):  
Vaccine Efficacy ◽  
Cox Regression ◽  
Simulated Data ◽  
Time Dependent ◽  
Vaccine Protection ◽  
Survival Analyses ◽  
Individual Level ◽  
Force Of Infection ◽  
Level Data ◽  
Over Time

AbstractFew methods exist to estimate vaccine efficacy and its decay following immunisation. Existing methods are largely based on survival analyses such as Poisson or Cox-regression, applied to individual-level data from randomised placebo-controlled trials (RCTs), however, such are often not easily available for analysing pooling evidence across trials. Hence, cumulative vaccine efficacy (VE), the commonly reported endpoint, is implicitly assumed a reasonable proxy for the instantaneous vaccine efficacy (iVE). This assumption is violated if the relative risk (RR) of vaccinated vs unvaccinated is not constant over time, i.e. if vaccine efficacy changes after immunisation. We propose a method to overcome this issue. We use estimates of VE stratified by time since completed immunisation, and estimate time-dependent iVE. We validate the method against simulated data for two forms of vaccine protection: all-or-nothing protection and leaky protection. We illustrate how VE estimates are biased by time-dependent effects in the baseline force of infection and in iVE. Our proposed method improves upon available iVE estimation techniques, particularly if the vaccine induced leaky-like protection and the disease outcome is rare.

scholarly journals Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

2021 ◽  
Author(s):  
Chris Davis ◽  
Nicola Logan ◽  
Grace Tyson ◽  
Richard Orton ◽  
William Harvey ◽  
...  
Keyword(s):  
South African ◽  
Vaccine Efficacy ◽  
Antigenic Drift ◽  
Productive Infection ◽  
Subsequent Reduction ◽  
Fold Reduction ◽  
Antibody Titres ◽  
Efficacy Assessment ◽  
Induced Immunity ◽  
Over Time

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.1351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

scholarly journals Assessing Durability of Vaccine Effect Following Blinded Crossover in COVID-19 Vaccine Efficacy Trials

2020 ◽  
Author(s):  
Dean Follmann ◽  
Jonathan Fintzi ◽  
Michael P. Fay ◽  
Holly E. Janes ◽  
Lindsey Baden ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Clinical Effectiveness ◽  
Late Enhancement ◽  
Open Label ◽  
Term Efficacy ◽  
Efficacy Trials ◽  
Timely Access ◽  
Over Time

ABSTRACTBackgroundSeveral candidate vaccines to prevent COVID-19 disease have entered large-scale phase 3 placebo-controlled randomized clinical trials and some have demonstrated substantial short-term efficacy. Efficacious vaccines should, at some point, be offered to placebo participants, which will occur before long-term efficacy and safety are known.MethodsFollowing vaccination of the placebo group, we show that placebo-controlled vaccine efficacy can be derived by assuming the benefit of vaccination over time has the same profile for the original vaccine recipients and the placebo crossovers. This reconstruction allows estimation of both vaccine durability and potential vaccine-associated enhanced disease.ResultsPost-crossover estimates of vaccine efficacy can provide insights about durability, identify waning efficacy, and identify late enhancement of disease, but are less reliable estimates than those obtained by a standard trial where the placebo cohort is maintained. As vaccine efficacy estimates for post-crossover periods depend on prior vaccine efficacy estimates, longer pre-crossover periods with higher case counts provide better estimates of late vaccine efficacy. Further, open-label crossover may lead to riskier behavior in the immediate crossover period for the unblinded vaccine arm, confounding vaccine efficacy estimates for all post-crossover periods.ConclusionsWe advocate blinded crossover and continued follow-up of trial participants to best assess vaccine durability and potential delayed enhancement of disease. This approach allows placebo recipients timely access to the vaccine when it would no longer be proper to maintain participants on placebo, yet still allows important insights about immunological and clinical effectiveness over time.

scholarly journals Temporal variations of country-specific mutational profile of SARS-CoV-2: effect on vaccine efficacy

2021 ◽  
pp. 00-00
Author(s):  
Sayantan Laha ◽  
Raghunath Chatterjee
Keyword(s):  
Vaccine Efficacy ◽  
Temporal Variations ◽  
Spike Protein ◽  
Protein Vaccine ◽  
Active Monitoring ◽  
Travel Restrictions ◽  
Different Levels ◽  
Over Time ◽  
Country Specific ◽  
New Mutations

Aim: In order to curb the transmission of SARS-CoV-2, nation-wide travel restrictions at different levels were implemented in different countries. Country-specific mutational profile may exist and have an impact on vaccine efficacy. Materials & methods: We identified nonsynonymous mutations in approximately 215,000 SARS-CoV-2 sequences during the 1st year of the pandemic in 35 countries. Mutational profiles on a bimonthly basis were traced over time. We also examined the mutations that overlapped with the spike protein vaccine epitopes. Results: Several new mutations emerged over time and were dominating in specific countries. Many nonsynonymous mutations were within multiple spike protein epitopes that might impact the vaccine efficacy. Conclusion: Our study advocates requirement of active monitoring of country-specific mutations and vaccine efficacies in respective countries.

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