scholarly journals Designing a Study of Correlates of Risk for Ebola Vaccination

2018 ◽  
Author(s):  
M. Elizabeth Halloran ◽  
Ira M. Longini ◽  
Peter B. Gilbert
Keyword(s):  
Vaccine Efficacy ◽  
Randomized Trials ◽  
Vaccination Campaign ◽  
Vaccine Protection ◽  
Vaccine Candidates ◽  
Vaccination Trial ◽  
Ring Vaccination ◽  
Risk Protection ◽  
Outbreak Situation

AbstractThe rVSV Ebola vaccine was shown to be very efficacious in a novel ring vaccination trial in Guinea. However, no correlates of vaccine protection have been established for Ebola vaccines. Several Ebola vaccine candidates are available, but conducting randomized trials of additional candidates in outbreak situations has become difficult. Establishing correlates of vaccine protection would be useful in helping vaccine candidates become licensed. In this note, we explore power and sample calculations to study potential correlates of risk (protection) during an Ebola vaccination campaign in an outbreak situation under a number of assumptions. At an overall vaccine efficacy of 75%, 50 Ebola endpoints in the vaccinees provided good power. At an overall vaccine efficacy of 90%, 20 Ebola endpoints gave good power under certain assumptions. In the May – July 2018 Ebola outbreak in DRC, over 3000 individuals were vaccinated, with no reported cases in vaccinated individuals. To be feasible, this type of study need Ebola endpoints in vaccinated individuals.

scholarly journals Designing a Study of Correlates of Risk for Ebola Vaccination

2020 ◽  
Vol 189 (8) ◽  
pp. 747-754 ◽  
Author(s):  
M Elizabeth Halloran ◽  
Ira M Longini ◽  
Peter B Gilbert
Keyword(s):  
Vaccine Efficacy ◽  
Vaccination Campaign ◽  
Blood Draw ◽  
Vaccine Protection ◽  
Ring Vaccination ◽  
Sample Size Calculations ◽  
Low Responder ◽  
Vesicular Stomatitis ◽  
Predetermined Time

Abstract The recombinant vesicular stomatitis virus (rVSV) Ebola vaccine was shown to be very efficacious in a novel ring vaccination trial in Guinea. However, no correlates of vaccine protection have been established for Ebola vaccines. Several Ebola vaccine candidates are available, but conducting randomized trials of additional candidates in outbreaks is difficult. Establishing correlates of vaccine protection is essential. Here we explore power and sample-size calculations to evaluate potential correlates of risk during an Ebola vaccination campaign in an outbreak. The method requires that a blood draw be made at a predetermined time after vaccination. The statistical analysis estimates the relative risk of the Ebola endpoint occurring from after the blood draw through to the end of follow-up, contrasting vaccine recipients with different values of the immune response marker. The analysis can be done assuming a trichotomous or continuous marker. Under certain assumptions, at an overall vaccine efficacy of 75%, 50 Ebola endpoints in the vaccinees provided good power. At an overall vaccine efficacy of 90%, 20 Ebola endpoints gave good power. Power was highest when more vaccinees were in the high- and low-responder groups versus the middle group and when vaccine efficacy differed the most between the high- and low-responder groups.

scholarly journals Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

2015 ◽  
Vol 23 (2) ◽  
pp. 84-94 ◽  
Author(s):  
David R. Martinez ◽  
Sallie R. Permar ◽  
Genevieve G. Fouda
Keyword(s):  
Immune Responses ◽  
Hiv Infection ◽  
Vaccine Efficacy ◽  
Neutralizing Antibody ◽  
Hiv Vaccine ◽  
Antibody Responses ◽  
Hiv Vaccines ◽  
Vaccine Candidates ◽  
Protective Antibodies ◽  
Pediatric Populations

ABSTRACTExtensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.

scholarly journals Malaria vaccines: lessons from field trials

1994 ◽  
Vol 10 (suppl 2) ◽  
pp. S310-S326 ◽  
Author(s):  
Claudio J. Struchiner ◽  
M. Elizabeth Halloran ◽  
Robert C. Brunet ◽  
José M. C. Ribeiro ◽  
Eduardo Massad
Keyword(s):  
Causal Inference ◽  
Vaccine Efficacy ◽  
Malaria Vaccine ◽  
Field Trials ◽  
Final States ◽  
Vaccine Candidates ◽  
Malaria Vaccines ◽  
Epidemiologic Data

Malaria vaccine candidates have already been tested and new trials are being carried out. We present a brief description of specific issues of validity that are relevant when assessing vaccine efficacy in the field and illustrate how the application of these principles might improve our interpretation of the data being gathered in actual malaria vaccine field trials. Our discussion assumes that vaccine evaluation shares the same general principles of validity with epidemiologic causal inference, i.e., the process of drawing inferences from epidemiologic data aiming at the identification of causes of diseases. Judicious exercise of these principles indicates that, for meaningful interpretation, measures of vaccine efficacy require definitions based upon arguments conditional on the amount of exposure to infection, and specification of the initial and final states in which one believes the effect of interest takes place.

scholarly journals The O-Ag Antibody Response to Francisella Is Distinct in Rodents and Higher Animals and Can Serve as a Correlate of Protection

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1646
Author(s):  
Lauren E. Shoudy ◽  
Prachi Namjoshi ◽  
Gabriela Giordano ◽  
Sudeep Kumar ◽  
Jennifer D. Bowling ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Low Dose ◽  
High Sensitivity ◽  
High Dose ◽  
Live Vaccine Strain ◽  
Plasma Samples ◽  
Vaccine Candidates ◽  
Correlates Of Protection ◽  
Vaccine Trials ◽  
Bona Fide

Identifying correlates of protection (COPs) for vaccines against lethal human (Hu) pathogens, such as Francisella tularensis (Ft), is problematic, as clinical trials are currently untenable and the relevance of various animal models can be controversial. Previously, Hu trials with the live vaccine strain (LVS) demonstrated ~80% vaccine efficacy against low dose (~50 CFU) challenge; however, protection deteriorated with higher challenge doses (~2000 CFU of SchuS4) and no COPs were established. Here, we describe our efforts to develop clinically relevant, humoral COPs applicable to high-dose, aerosol challenge with S4. First, our serosurvey of LVS-vaccinated Hu and animals revealed that rabbits (Rbs), but not rodents, recapitulate the Hu O-Ag dependent Ab response to Ft. Next, we assayed Rbs immunized with distinct S4-based vaccine candidates (S4ΔclpB, S4ΔguaBA, and S4ΔaroD) and found that, across multiple vaccines, the %O-Ag dep Ab trended with vaccine efficacy. Among S4ΔguaBA-vaccinated Rbs, the %O-Ag dep Ab in pre-challenge plasma was significantly higher in survivors than in non-survivors; a cut-off of >70% O-Ag dep Ab predicted survival with high sensitivity and specificity. Finally, we found this COP in 80% of LVS-vaccinated Hu plasma samples as expected for a vaccine with 80% Hu efficacy. Collectively, the %O-Ag dep Ab response is a bona fide COP for S4ΔguaBA-vaccinated Rb and holds significant promise for guiding vaccine trials with higher animals.

Third Shot vaccination for COVID-19 in Israel

2021 ◽  
Vol 6 ◽  
Keyword(s):  
Clinical Trials ◽  
Vaccine Efficacy ◽  
Vaccination Campaign ◽  
Vaccine Delivery ◽  
Vaccine Effectiveness ◽  
High Quality ◽  
Equitable Distribution ◽  
Correlates Of Protection ◽  
Scientific Questions ◽  
Global Population

After several manufacturers announced COVID-19 vaccine efficacy in clinical trials for disease, a comprehensive post-efficacy strategy for the following steps to ensure vaccination of the global population is now required. These considerations should include: how to manufacture billions of doses of high-quality vaccines, support for vaccine purchase, coordination of supply, the equitable distribution of vaccines, and the logistics of global vaccine delivery, all of which are a prelude to a massive vaccination campaign targeting people of all ages. Furthermore, additional scientific questions about the vaccines remain, and that should be answered to improve vaccine efficacy, including questions regarding the optimization of vaccination regimens, booster doses, the correlates of protection, vaccine effectiveness, safety, and enhanced surveillance. The timely and coordinated execution of these post-efficacy tasks will bring the pandemic effective and efficient [1].

scholarly journals Primary COVID-19 vaccine cycle and booster doses efficacy: analysis of Italian nationwide vaccination campaign

2021 ◽  
Author(s):  
Giuseppe Lippi ◽  
Camilla Mattiuzzi
Keyword(s):  
Vaccine Efficacy ◽  
Vaccination Campaign ◽  
Efficacy Analysis ◽  
Vaccine Booster

Abstract We provide here an updated analysis of primary COVID-19 vaccination and vaccine booster doses efficacy, emerging from the ongoing Italian nationwide COVID-19 vaccination campaign. Primary COVID-19 vaccination efficacy was 76-92% within 6 months, decreasing to 34-80% after 6 months. Administration of vaccine booster doses decreased SARS-CoV-2 infections by 65%, COVID-19 related hospitalizations and deaths by 69% and 97% compared to vaccine efficacy after 6 months, but also decreased SARS-CoV-2 infections by 39% compared to vaccine efficacy within 6 months. These results suggest that COVID-19 vaccine booster doses are important for restoring vaccine efficacy and further limiting virus circulation.

scholarly journals Monocyte-derived transcriptome signature indicates antibody-dependent cellular 1 phagocytosis as the primary mechanism of vaccine-induced protection against HIV-1

2021 ◽  
Author(s):  
Shida Shangguan ◽  
Philip K Ehrenberg ◽  
Aviva Geretz ◽  
Lauren Yum ◽  
Gautam Kundu ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Single Cells ◽  
Vaccine Trial ◽  
Gene Signature ◽  
Potential Mechanism ◽  
Protein Vaccine ◽  
Vaccine Protection ◽  
Effector Cells ◽  
Hiv 1 ◽  
Transcriptome Signature

A gene signature previously correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus (SIV) and SHIV challenge models in non-human primates (NHP). In this report we investigated presence of this signature as a correlate of reduced risk in human clinical trials and potential mechanism for protection. The absence of this gene signature in the DNA/rAd5 human vaccine trial which did not show efficacy, strengthens our hypothesis that this signature is only enriched in studies that demonstrated protection. This gene signature was enriched in the partially effective RV144 human trial that administered the ALVAC/protein vaccine, and we find that the signature associates with both decreased risk of HIV-1 acquisition and increased vaccine efficacy. Total RNA-seq in a clinical trial that used the same vaccine regimen as the RV144 HIV vaccine implicated antibody-dependent cellular phagocytosis (ADCP) as a potential mechanism of vaccine protection. CITE-seq profiling of 53 surface markers and transcriptomes of 53,777 single cells from the same trial, showed that genes in this signature were primarily expressed in cells belonging to the myeloid lineage including monocytes, which are major effector cells for ADCP. The consistent association of this transcriptome signature with vaccine efficacy represents a tool both to identify potential mechanisms, as with ADCP here, and to screen novel approaches to accelerate development of new vaccine candidates.

scholarly journals Assessing the feasibility of Nipah vaccine efficacy trials based on previous outbreaks in Bangladesh

2020 ◽  
Author(s):  
Birgit Nikolay ◽  
Marc Lipsitch ◽  
Mahmudur Rahman ◽  
Stephen P. Luby ◽  
Henrik Salje ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Time Window ◽  
Nipah Virus ◽  
Vaccine Trial ◽  
Cluster Randomized Trial ◽  
Case Control ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Ring Vaccination ◽  
Cluster Randomized

AbstractBackgroundNipah virus (NiV) is an emerging, bat-borne pathogen that can be transmitted from person-to-person. Vaccines are currently being developed for NiV, and studies funded to evaluate their safety and immunogenicity, so that they could possibly be used to contain outbreaks. An important unanswered question is whether it will be possible to evaluate the efficacy of vaccine candidates in phase III clinical trials in a context where spillovers from the zoonotic reservoir are infrequent and associated with small outbreaks. The objective of this study was to investigate the feasibility of conducting a phase III vaccine trial in Bangladesh, the only country reporting regularly NiV cases.MethodsWe used simulations based on previously observed NiV cases from Bangladesh, an assumed vaccine efficacy of 90% and other NiV vaccine target characteristics, to compare three vaccination study designs: (i) cluster randomized ring vaccination, (ii) cluster randomized mass vaccination, and (iii) an observational case-control study design.ResultsThe simulations showed that, assuming a ramp-up period of 10 days and a mean hospitalization delay of 4 days, it would take 516 years and over 163,000 vaccine doses to run a ring vaccination trial under current epidemic conditions. A cluster-randomized trial in the two most affected districts would take 81 years and 2.3 million vaccine doses. An observational case-control design in these two districts would require seven years and 2.5 million vaccine doses.DiscussionWithout a change in the epidemiology of NiV, ring vaccination or cluster-randomized trials are unlikely to be completed within a reasonable time window. In this light, the remaining options are: (i) not conducting a phase III trial until the epidemiology of NiV changes, (ii) identifying alternative ways to licensure such as observational studies or controlled studies in animals such as in the US Food and Drug Administration’s (FDA) Animal Rule.

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