Vaccine Response Impaired
Conditions
Keywords
Vaccine Hyporesponse
Brief summary
This study evaluated whether it is possible in healthy elderly participants to generate baseline biomarker-based prediction rules (PdR) for vaccine response (post baseline absolute serum antibody titer) using each of the protocol selected vaccines separately; and examined the rank correlation coefficients of pairs of post vaccination antibody titers within the same elderly individuals.
Interventions
BIOLOGICALTetanus & Diphtheria booster vaccine (Td)
Tetanus & Diphtheria booster vaccine (Td), single intramuscular dose
BIOLOGICALTwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]
TwinrixTM \[Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine\], intramuscular, two doses of standard three dose regimen (opposite arms)
BIOLOGICALDukoral® Traveler's Diarrhea Vaccine (WC/rBS)
Dukoral® Traveler's Diarrhea Vaccine, recombinant Cholera toxin B subunit (WC/rBS), standard two oral doses per treatment regimen
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female aged 25 to 40 years old or 65 years of age or older at the prestudy (screening) visit * Has no fever on day of screening * Lacks Hepatitis B surface antigen seroreactivity * If female 25 to 40 years of age, is not pregnant nor breastfeeding, and agrees to use effective contraception
Exclusion criteria
* Has a prior history of Hepatitis B Virus infection * Has BMI (Body Mass Index) \>35 * If female 25 to 40 years of age, is pregnant, or expecting to conceive, donate eggs or breastfeed * Has received immune globulin and/or blood products within 3 months prior to first dose received * Has a history of immunosuppression resulting from disease (e.g., malignancy; human immunodeficiency virus \[HIV\] infection), or is currently taking corticosteroids or other immunosuppressive/cytotoxic therapy (cancer chemotherapy or organ transplantation) * Has an active neoplastic disease * Has had any infection including upper respiratory viral syndrome in the 6 weeks prior to planned collection of baseline laboratory samples * Has received a live virus vaccine or an inactivated vaccine or is scheduled to receive a live virus vaccine or an inactivated vaccine in the period from 6 weeks prior to receipt of the first vaccine through the completion of all study visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. | 3 weeks or 1 month after each final vaccination | Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to each of these four antigens were then measured 1 month after each final vaccination (3 weeks for cholera toxin), based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). |
| Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Baseline and 1 month after final vaccination | Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on enzyme linked immunosorbent assay (ELISA), and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by messenger RNA (mRNA) profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln). |
| Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Baseline and 1 month after final vaccination | Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln). |
| Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Baseline and 1 month after final vaccination | Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln). |
| Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Baseline and 3 weeks after final vaccination | Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Day 7 and 1 month after each final vaccination | Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln). |
| Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Day 7 and 1 month after final vaccination | Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln). |
| Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Day 7 and 3 weeks after final vaccination | Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln). |
| Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Day 7 and 1 month after final vaccination | Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected at 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Younger Participants Aged 25 to 40 years old | 30 |
| Elderly Participants Aged 65 years and older | 144 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Younger Participants | Elderly Participants | Total |
|---|---|---|---|
| Age, Continuous | 33.9 Years STANDARD_DEVIATION 3.6 | 70.2 Years STANDARD_DEVIATION 4.1 | 63.9 Years STANDARD_DEVIATION 14.3 |
| Sex: Female, Male Female | 18 Participants | 77 Participants | 95 Participants |
| Sex: Female, Male Male | 12 Participants | 67 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 174 |
| serious Total, serious adverse events | 0 / 174 |
Outcome results
Primary
Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.
Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on enzyme linked immunosorbent assay (ELISA), and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by messenger RNA (mRNA) profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).
Time frame: Baseline and 1 month after final vaccination
Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Participants | Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Predicted Titer | 2.27 ln International Units | Standard Deviation 1.24 |
| Elderly Participants | Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Measured Titer | 2.12 ln International Units | Standard Deviation 1.91 |
Comparison: Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \<= 20%; whereas the alternative hypothesis is \> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all baseline biomarkers as predictors.95% CI: [-13.8, -0.7]
Primary
Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.
Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).
Time frame: Baseline and 3 weeks after final vaccination
Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Participants | Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Predicted Titer | 5.24 ln International Units | Standard Deviation 0.99 |
| Elderly Participants | Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Measured Titer | 5.20 ln International Units | Standard Deviation 1.55 |
Comparison: Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \<= 20%; whereas the alternative hypothesis is \> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all baseline biomarkers as predictors.95% CI: [-2.8, 8.5]
Primary
Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.
Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).
Time frame: Baseline and 1 month after final vaccination
Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Participants | Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Predicted Titer | -0.43 ln International Units | Standard Deviation 1.25 |
| Elderly Participants | Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Measured Titer | -0.46 ln International Units | Standard Deviation 1.77 |
Comparison: Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \<= 20%; whereas the alternative hypothesis is \> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all baseline biomarkers as predictors.95% CI: [19.6, 32.4]
Primary
Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.
Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).
Time frame: Baseline and 1 month after final vaccination
Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Participants | Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Predicted Titer | 1.40 ln International Units | Standard Deviation 1.24 |
| Elderly Participants | Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. | Measured Titer | 1.32 ln International Units | Standard Deviation 1.84 |
Comparison: Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \<= 20%; whereas the alternative hypothesis is \> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all baseline biomarkers as predictors.95% CI: [10.6, 20.9]
Primary
Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants.
Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to each of these four antigens were then measured 1 month after each final vaccination (3 weeks for cholera toxin), based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln).
Time frame: 3 weeks or 1 month after each final vaccination
Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Participants | Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. | Hepatitis B | 2.12 ln International Units | Standard Deviation 1.91 |
| Elderly Participants | Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. | Tetanus | 1.32 ln International Units | Standard Deviation 1.84 |
| Elderly Participants | Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. | Diphtheria | -0.46 ln International Units | Standard Deviation 1.77 |
| Elderly Participants | Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. | Cholera | 5.20 ln International Units | Standard Deviation 1.55 |
Comparison: Diphtheria versus Hepatitis Bp-value: 0.6695% CI: [-0.2, 0.13]Fisher's Z-transformation
Comparison: Diphtheria versus Cholerap-value: 0.2695% CI: [-0.07, 0.25]Fisher's Z-transformation
Comparison: Diphtheria versus Tetanusp-value: <0.00195% CI: [0.26, 0.53]Fisher's Z-transformation
Comparison: Hepatitis B versus Cholerap-value: 0.0495% CI: [-0.32, -0.01]Fisher's Z-transformation
Comparison: Hepatitis B versus Tetanusp-value: 0.395% CI: [-0.25, 0.08]Fisher's Z-transformation
Comparison: Cholera versus Tetanusp-value: 0.3695% CI: [-0.09, 0.24]Fisher's Z-transformation
Secondary
Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.
Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected at 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).
Time frame: Day 7 and 1 month after final vaccination
Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Participants | Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Predicted Titer | 2.25 ln International Units | Standard Deviation 1.24 |
| Elderly Participants | Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Measured Titer | 2.12 ln International Units | Standard Deviation 1.91 |
Comparison: Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \<= 20%; whereas the alternative hypothesis is \> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all Day 7 biomarkers as predictors.95% CI: [-16.6, -2.7]
Secondary
Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.
Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).
Time frame: Day 7 and 3 weeks after final vaccination
Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Participants | Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Predicted Titer | 5.24 ln International Units | Standard Deviation 0.96 |
| Elderly Participants | Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Measured Titer | 5.20 ln International Units | Standard Deviation 1.55 |
Comparison: Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \<= 20%; whereas the alternative hypothesis is \> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all Day 7 biomarkers as predictors.95% CI: [-7.8, 4.4]
Secondary
Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.
Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).
Time frame: Day 7 and 1 month after final vaccination
Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Participants | Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Predicted Titer | -0.37 ln International Units | Standard Deviation 1.36 |
| Elderly Participants | Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Measured Titer | -0.46 ln International Units | Standard Deviation 1.77 |
Comparison: Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \<= 20%; whereas the alternative hypothesis is \> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all Day 7 biomarkers as predictors.95% CI: [28.7, 41.5]
Secondary
Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.
Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized international units of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).
Time frame: Day 7 and 1 month after each final vaccination
Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Elderly Participants | Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Predicted Titer | 1.43 ln International Units | Standard Deviation 1.27 |
| Elderly Participants | Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. | Measured Titer | 1.32 ln International Units | Standard Deviation 1.84 |
Comparison: Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \<= 20%; whereas the alternative hypothesis is \> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all Day 7 biomarkers as predictors.95% CI: [14, 29.7]