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This study is to assess the safety and immunogenicity of three consecutive lots of JE-CV in toddlers aged 12-18 months.
Primary objective:
To demonstrate the bio-equivalence of three lots of JE-CV vaccine manufactured by sanofi pasteur.
Secondary objective:
To describe the safety of vaccination in all subjects
This is a Phase III trial in toddlers in Thailand and the Philippines.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| JE-CV GPO MBP (Lot 1) | Experimental | Participants 12 to 18 months of age received one dose of Japanese encephalitis chimeric virus vaccine (JE-CV) from Government Pharmaceutical Organization Mérieux Biological Products (GPO-MBP) Lot 1. |
|
| JE-CV GPO MBP (Lot 2) | Experimental | Participants 12 to 18 months of age received one dose of Japanese encephalitis chimeric virus vaccine (JE-CV) from Government Pharmaceutical Organization Mérieux Biological Products (GPO-MBP) Lot 2. |
|
| JE-CV GPO MBP (Lot 3) | Experimental | Participants 12 to 18 months of age received one dose of Japanese encephalitis chimeric virus vaccine (JE-CV) from Government Pharmaceutical Organization Mérieux Biological Products (GPO-MBP) Lot 3. |
|
| JE-CV WRAIR (Group 4) | Active Comparator | Participants 12 to 18 months of age received one dose of JE-CV from Acambis at Walter Reed Army Institute of Research (WRAIR) |
|
| Hepatitis A (Group 5) | Sham Comparator | Participants 12 to 18 months of age randomized to receive Hepatitis A vaccine |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Japanese encephalitis vaccine | Biological | 0.5 mL, Subcutaneous |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Seroconversion to Vaccine Antigens Following Vaccination With JE-CV by GPO MBP Lots | Anti-Japanese encephalitis chimeric virus vaccine antibodies were measured using the 50% plaque reduction neutralization test (PRNT50). Seroconversion was defined as participants with a pre-vaccination titer <10 1/dil and post-vaccination titer ≥ 10 1/dil, or participants with pre-vaccination titer ≥ 10 1/dil and 4-fold increase from pre- to post-vaccination. | Day 0 (pre-vaccination) and Day 28 post-vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Titers Against the Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) Antigens Before and Following Vaccination With a JE-CV by GPO MBP Lot or Walter Reed Army Institute of Research (WRAIR) JE-CV | Anti-Japanese Encephalitis Chimeric Virus antibodies were measured using the 50% plaque reduction neutralization test (PRNT50) assay. | Day 0 (pre-vaccination) and Day 28 post-vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| Serological Status of Flavivirus Infection at Baseline (Before) Vaccination With a Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Hepatitis A Vaccine. | Flavivirus (FV) positive was defined as anti-JE against homologous virus strain ≥10 l/dil or anti dengue against at least one serotype ≥10 l/dil. FV negative was defined as anti-JE against homologous virus strain <10 l/dil and anti-dengue against the 4 serotypes <10 l/dilution. |
Inclusion Criteria :
Exclusion Criteria :
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Sanofi Pasteur Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alabang | Philippines | |||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22777096 | Result | Feroldi E, Pancharoen C, Kosalaraksa P, Watanaveeradej V, Phirangkul K, Capeding MR, Boaz M, Gailhardou S, Bouckenooghe A. Single-dose, live-attenuated Japanese encephalitis vaccine in children aged 12-18 months: randomized, controlled phase 3 immunogenicity and safety trial. Hum Vaccin Immunother. 2012 Jul;8(7):929-37. doi: 10.4161/hv.20071. Epub 2012 Jul 1. | |
| 24656175 |
| Label | URL |
|---|---|
| Related Info | View source |
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A total of 1200 participants who met all of the inclusion and none of the exclusion criteria were randomized, 1199 were vaccinated in this study.
The study participants were enrolled from 02 August 2008 through 27 March 2009 at 3 clinic sites in Thailand and 5 clinic sites in the Philippines.
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| ID | Title | Description |
|---|---|---|
| FG000 | JE-CV GPO MBP (Lot 1) | Participants 12 to 18 months of age received one dose of Japanese encephalitis chimeric virus vaccine (JE-CV) from Government Pharmaceutical Organization Mérieux Biological Products (GPO-MBP) Lot 1. |
| FG001 | JE-CV GPO MBP (Lot 2) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| Japanese encephalitis vaccine | Biological | 0.5 mL, Subcutaneous |
|
|
| Japanese encephalitis vaccine | Biological | 0.5 mL, Subcutaneous |
|
|
| Japanese encephalitis vaccine (Acambis) | Biological | 0.5 mL, Subcutaneous |
|
| Hepatitis A vaccine | Biological | 0.5 mL, Intramuscular |
|
|
| Number of Participants With Seroprotection to Japanese Encephalitis Chimeric Virus Antigens Before and Following Vaccination With a JE-CV by GPO MBP Lot or WRAIR JE-CV | Anti-Japanese encephalitis chimeric virus vaccine antibodies were measured using the PRNT50 assay. Seroprotection was defined as the proportion of subjects with a JE CV virus PRNT50 neutralizing antibody titer ≥10 1/dilution (dil). | Day 0 (pre-vaccination) and Day 28 post-vaccination |
| Geometric Mean Titers Ratios Against the Japanese Encephalitis Chimeric Virus (JE-CV) Antigen Following Vaccination With One of the JE-CV by GPO MBP Lots or WRAIR JE-CV Vaccine | Anti Japanese encephalitis chimeric virus antibodies were measured using the PRNT50 assay. | Day 0 (pre-vaccination) and Day 28 post-vaccination |
| Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With a Japanese Encephalitis Chimeric Virus Vaccine (JE- CV) by GPO MBP Lot or WRAIR JE-CV, or Hepatitis A Vaccine. | Solicited injection site: Tenderness, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, and Irritability. Grade 3 injection site: Tenderness, cries when injected limb is moved or the movement of injected limb is reduced; Erythema and Swelling ≥5 cm. Grade 3 systemic reactions: Fever, temperature >39.5˚C; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying Abnormal, >3 hours; Drowsiness, sleeping most of the time or difficult to wake up; Appetite Lost, refuses ≥3 or most feeds/meals; and Irritability, inconsolable. | Day 0 up to Day 14 post-vaccination |
| Day 0 (pre-vaccination) |
| Bayanan |
| Philippines |
| Buli | Philippines |
| Cupang | Philippines |
| Sucat | Philippines |
| Bangkok | 10330 | Thailand |
| Bangkok | 10400 | Thailand |
| Khon Kaen | 40002 | Thailand |
| Bonaparte M, Dweik B, Feroldi E, Meric C, Bouckenooghe A, Hildreth S, Hu B, Yoksan S, Boaz M. Immune response to live-attenuated Japanese encephalitis vaccine (JE-CV) neutralizes Japanese encephalitis virus isolates from south-east Asia and India. BMC Infect Dis. 2014 Mar 21;14:156. doi: 10.1186/1471-2334-14-156. |
Participants 12 to 18 months of age received one dose of JE-CV from GPO MBP Lot 2 |
| FG002 | JE-CV GPO MBP (Lot 3) | Participants 12 to 18 months of age received one dose of JE- CV from GPO MBP Lot 3 |
| FG003 | JE-CV WRAIR | Participants 12 to 18 months of age received one dose of JE-CV from Acambis at Walter Reed Army Institute of Research (WRAIR) |
| FG004 | Hepatitis A | Participants 12 to 18 months of age received the Hepatitis A vaccine |
| COMPLETED |
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| NOT COMPLETED |
|
|
The baseline analysis population represents the participants who have received the trial vaccine or control vaccine (safety analysis set). Data on participants were analyzed and presented according to the vaccine they actually received.
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| ID | Title | Description |
|---|---|---|
| BG000 | JE CV GPO MBP (Lot 1) | Participants 12 to 18 months of age received one dose of Japanese encephalitis chimeric virus vaccine (JE CV) from Government Pharmaceutical Organization Mérieux Biological Products (GPO MBP) Lot 1 subcutaneously |
| BG001 | JE-CV GPO MBP (Lot 2) | Participants 12 to 18 months of age received one dose of JE-CV from GPO MBP Lot 2 |
| BG002 | JE-CV GPO MBP (Lot 3) | Participants 12 to 18 months of age received one dose of JE-CV from GPO MBP Lot 3 |
| BG003 | JE-CV WRAIR | Participants 12 to 18 months of age received one dose of JE-CV from Acambis at Walter Reed Army Institute of Research (WRAIR) |
| BG004 | Hepatitis A | Participants 12 to 18 months of age received Hepatitis A vaccine |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | Months |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Seroconversion to Vaccine Antigens Following Vaccination With JE-CV by GPO MBP Lots | Anti-Japanese encephalitis chimeric virus vaccine antibodies were measured using the 50% plaque reduction neutralization test (PRNT50). Seroconversion was defined as participants with a pre-vaccination titer <10 1/dil and post-vaccination titer ≥ 10 1/dil, or participants with pre-vaccination titer ≥ 10 1/dil and 4-fold increase from pre- to post-vaccination. | Seroconversion to the JE CV vaccine antigens was assessed in the participants who were vaccinated and completed all study defined activities, Per-Protocol Analysis Set. | Posted | Number | Participants | Day 0 (pre-vaccination) and Day 28 post-vaccination |
|
|
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean Titers Against the Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) Antigens Before and Following Vaccination With a JE-CV by GPO MBP Lot or Walter Reed Army Institute of Research (WRAIR) JE-CV | Anti-Japanese Encephalitis Chimeric Virus antibodies were measured using the 50% plaque reduction neutralization test (PRNT50) assay. | Geometric mean titers against the JE CV antigens were assessed in the participants who were vaccinated and completed all study defined activities, Per-Protocol Analysis Set. | Posted | Geometric Mean | 95% Confidence Interval | Titers | Day 0 (pre-vaccination) and Day 28 post-vaccination |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Seroprotection to Japanese Encephalitis Chimeric Virus Antigens Before and Following Vaccination With a JE-CV by GPO MBP Lot or WRAIR JE-CV | Anti-Japanese encephalitis chimeric virus vaccine antibodies were measured using the PRNT50 assay. Seroprotection was defined as the proportion of subjects with a JE CV virus PRNT50 neutralizing antibody titer ≥10 1/dilution (dil). | Seroprotection against JE CV antigens was assessed in the participants who were vaccinated and completed all study defined activities, Per-Protocol Analysis Set. | Posted | Number | Participants | Day 0 (pre-vaccination) and Day 28 post-vaccination |
| ||||||||||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean Titers Ratios Against the Japanese Encephalitis Chimeric Virus (JE-CV) Antigen Following Vaccination With One of the JE-CV by GPO MBP Lots or WRAIR JE-CV Vaccine | Anti Japanese encephalitis chimeric virus antibodies were measured using the PRNT50 assay. | Geometric mean titers against the JE CV antigens were assessed in the Per Protocol Analysis Set. | Posted | Geometric Mean | 95% Confidence Interval | Titer ratio | Day 0 (pre-vaccination) and Day 28 post-vaccination |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With a Japanese Encephalitis Chimeric Virus Vaccine (JE- CV) by GPO MBP Lot or WRAIR JE-CV, or Hepatitis A Vaccine. | Solicited injection site: Tenderness, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, and Irritability. Grade 3 injection site: Tenderness, cries when injected limb is moved or the movement of injected limb is reduced; Erythema and Swelling ≥5 cm. Grade 3 systemic reactions: Fever, temperature >39.5˚C; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying Abnormal, >3 hours; Drowsiness, sleeping most of the time or difficult to wake up; Appetite Lost, refuses ≥3 or most feeds/meals; and Irritability, inconsolable. | Solicited injection site and systemic reactions were assessed in the Safety Analysis Set. A participant randomized to receive JE CV GPO MBP Lot 1 vaccine, received JE CV GPO MBP Lot 3. For safety analysis, the participant was analyzed according to the actual vaccine received. | Posted | Number | Participants | Day 0 up to Day 14 post-vaccination |
| ||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Serological Status of Flavivirus Infection at Baseline (Before) Vaccination With a Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Hepatitis A Vaccine. | Flavivirus (FV) positive was defined as anti-JE against homologous virus strain ≥10 l/dil or anti dengue against at least one serotype ≥10 l/dil. FV negative was defined as anti-JE against homologous virus strain <10 l/dil and anti-dengue against the 4 serotypes <10 l/dilution. | Serological status of Flavivirus infection was assessed in the Per-protocol Analysis Set. | Posted | Number | Participants | Day 0 (pre-vaccination) |
|
Adverse events (AE) data were collected from Day 0 (post-vaccination) up to Day 180 post-vaccination.
The total (N) for solicited AEs in the table reflects participants for which diary cards were returned and with available data for the event during the period. A participant randomized to receive JE CV GPO MBP Lot 1 vaccine, received JE CV GPO MBP Lot 3. For safety analysis, the participant was analyzed according to the actual vaccine received.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | JE-CV GPO MBP (Lot 1) | Participants 12 to 18 months of age received one dose of Japanese encephalitis chimeric virus vaccine (JE CV) from Government Pharmaceutical Organization Mérieux Biological Products (GPO MBP) Lot 1 | 10 | 302 | 91 | 302 | ||
| EG001 | JE-CV GPO MBP (Lot 2) | Participants 12 to 18 months of age received one dose of JE-CV from GPO MBP Lot 2 | 17 | 299 | 99 | 299 | ||
| EG002 | JE-CV GPO MBP (Lot 3) | Participants 12 to 18 months of age received one dose of JE-CV from GPO MBP Lot 3 | 13 | 297 | 87 | 297 | ||
| EG003 | JE-CV WRAIR | Participants 12 to 18 months of age received one dose of JE-CV from Acambis at Walter Reed Army Institute of Research (WRAIR) | 7 | 199 | 65 | 199 | ||
| EG004 | Hepatitis A | Participants 12 to 18 months of age received Hepatitis A vaccine | 7 | 102 | 36 | 102 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchiolitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Febrile convulsion | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
| |
| Amoebiasis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Pneumonia viral | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Varicella | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Testicular yolk sac tumour stage III | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.0 | Non-systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA 10.0 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| |
| Injection site tenderness | General disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Injection site swelling | General disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Fever | General disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Crying Abnormal | Psychiatric disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Drowsiness | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Appetite Lost | Metabolism and nutrition disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA 10.0 | Systematic Assessment |
|
Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Sanofi Pasteur Inc. | RegistryContactUs@sanofipasteur.com |
| ID | Term |
|---|---|
| D004672 | Encephalitis, Japanese |
| D006506 | Hepatitis A |
| ID | Term |
|---|---|
| D004671 | Encephalitis, Arbovirus |
| D018792 | Encephalitis, Viral |
| D020805 | Central Nervous System Viral Diseases |
| D002494 | Central Nervous System Infections |
| D007239 | Infections |
| D000069544 | Infectious Encephalitis |
| D001102 | Arbovirus Infections |
| D000079426 | Vector Borne Diseases |
| D000096724 | Mosquito-Borne Diseases |
| D014777 | Virus Diseases |
| D012327 | RNA Virus Infections |
| D018177 | Flavivirus Infections |
| D018178 | Flaviviridae Infections |
| D004660 | Encephalitis |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000090862 | Neuroinflammatory Diseases |
| D006525 | Hepatitis, Viral, Human |
| D004769 | Enterovirus Infections |
| D010850 | Picornaviridae Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
Not provided
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| ID | Term |
|---|---|
| D022321 | Japanese Encephalitis Vaccines |
| D022362 | Hepatitis A Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D014761 | Viral Hepatitis Vaccines |
Not provided
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| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Philippines |
|
| JE CV Day 28 (≥10 1/dil; N=288, 284, 283, 192, 0) |
|
| OG003 |
| JE-CV WRAIR |
Participants 12 to 18 months of age received one dose of JE-CV from Acambis at Walter Reed Army Institute of Research (WRAIR) |
| OG004 | Hepatitis A | Participants 12 to 18 months of age received Hepatitis A vaccine |
|
|
| OG003 |
| JE-CV WRAIR |
Participants 12 to 18 months of age received one dose of JE-CV from Acambis at Walter Reed Army Institute of Research (WRAIR) |
| OG004 | Hepatitis A | Participants 12 to 18 months of age received Hepatitis A vaccine |
|
|
Participants 12 to 18 months of age received one dose of JE CV from Acambis at WRAIR subcutaneously |
| OG004 | Hepatitis A | Participants 12 to 18 months of age received the Hepatitis vaccine intramuscularly |
|
|
Participants 12 to 18 months of age received one dose of JE-CV from GPO MBP Lot 2
| OG002 | JE-CV GPO MBP (Lot 3) | Participants 12 to 18 months of age received one dose of JE-CV from GPO MBP Lot 3 |
| OG003 | JE-CV WRAIR | Participants 12 to 18 months of age received one dose of JE-CV from Acambis at Walter Reed Army Institute of Research (WRAIR) |
| OG004 | Hepatitis A | Participants 12 to 18 months of age received Hepatitis A vaccine |
|
|
| JE-CV WRAIR |
Participants 12 to 18 months of age received one dose of JE-CV from Acambis at Walter Reed Army Institute of Research (WRAIR) |
| OG004 | Hepatitis A | Participants 12 to 18 months of age received Hepatitis A vaccine |
|
|