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This trial will evaluate the safety and immunogenicity of: i) measles vaccine (CAM-70) after primary dose at 6 months (MV1) and booster vaccination at 12 months (MV2); ii) a single dose of varicella vaccination at 18 months; and iii) a single dose of hepatitis-A vaccination at 18 months in HIV-exposed and HIV-unexposed South African children.
Measles vaccine (MV) can reduce childhood mortality and is currently recommended to all South African children aged 6 months. Only one study has examined the safety and immunogenicity of the recommended CAM-70 measles vaccine strain in children under 9 months of age. In addition, there are limited data on the safety and immunogenicity of varicella vaccine (VV) and Hepatitis-A vaccination (Hep-AV) in HIV-exposed and HIV-unexposed children in Sub-Saharan Africa.
This is a prospective, observational cohort study nested within a larger randomized, open-label trial on pneumococcal-conjugate vaccine (PCV) titled PCV1+1. 70 HIV-exposed and 200 HIV-unexposed children will be enrolled at Chris Hani Baragwanath Academic Hospital (CHBAH) and neighbouring primary health clinics.
Immune responses to the vaccines will be measured as rate of seroconversion, rate of seroprotection, and geometric mean titres (GMT) one month post primary immunization (MV1, VV, Hep-AV) and one month post booster dose (MV2). In addition, pre-vaccination and medium long-term antibody levels at 4.5 months, 12 months and 18 months will be evaluated. Number of adverse events in all immunized infants will be recorded throughout the study duration and compared between groups. Long-term antibody levels at 3, 4 and 5 years of age will be measured during annual follow-up visits.
This study will add to the current evidence on immunizing infants with MV (CAM-70) at 6 and 12 months of age. Data will be stratified by HIV-exposure and HIV-infection, thereby offering insight in the influence of HIV on post-vaccination immune responses. The findings on VV/Hep-AV safety, immunogenicity and seroprevalence will be useful to informing future immunization policies in Sub-Saharan Africa.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HIV-unexposed children | Other | HIV-unexposed children enrolled in a randomized open label study on the pneumococcal conjugate vaccine (PCV1+1) will be invited to participate in this study. Children enrolled in the PCV1+1 study will receive all vaccines included in the South African public immunization program. Measles vaccine (0.5 mL, subcutaneous injection) will be adminstered at 6 months of age and 12 months of age. Varicella vaccine (0.5 mL, subcutaneous injection) or Hepatitis-A vaccine (0.5 mL, intra-muscular injection) will be administered to the participants at 18 months of age as an additional benefit for participating in the study. |
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| HIV-exposed children | Other | A cohort of HIV-exposed children will be recruited. Measles vaccine (0.5 mL, subcutaneous injection) will be adminstered at 6 months of age and 12 months of age. Varicella vaccine (0.5 mL, subcutaneous injection) or Hepatitis-A vaccine (0.5 mL, intra-muscular injection) will be administered to the participants at 18 months of age as an additional benefit for participating in the study. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Measles vaccine | Biological | All participants will receive measles vaccine at 6 and 12 months of age, according to the South African immunization schedule. All study vaccines are currently licensed in South Africa and will be administered according to their approved dosages, formulations and indications. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with seroprotective antibody titres (IgG ≥330 mIU/ml quantified by ELISA) one month post booster measles vaccination | Measured as seroprotection rate one month post booster measles vaccine in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children. | 13 months of age (one month post booster measles vaccine) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with seroprotective antibody titres (IgG ≥300 mIU/ml quantified by ELISA) one month post varicella vaccination | Measured as seroprotection rate one month post varicella immunization in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children. | 19 months of age (one month post vaccination) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shabir A Madhi, MD, PhD | University of Witwatersrand, South Africa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chris Hani Baragwanath Academic Hospital; Nrf/Dst Vpd Rmpru | Soweto | Gauteng | 2013 | South Africa |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38637212 | Derived | Mutsaerts EAML, van Cranenbroek B, Madhi SA, Simonetti E, Arns AJ, Jose L, Koen A, van Herwaarden AE, de Jonge MI, Verhagen LM. Impact of nutritional status on vaccine-induced immunity in children living in South Africa: Investigating the B-cell repertoire and metabolic hormones. Vaccine. 2024 May 22;42(14):3337-3345. doi: 10.1016/j.vaccine.2024.04.034. Epub 2024 Apr 17. | |
| 32307279 |
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Currently no plan to share IPD.
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| ID | Term |
|---|---|
| D008457 | Measles |
| D002644 | Chickenpox |
| D006506 | Hepatitis A |
| ID | Term |
|---|---|
| D018185 | Morbillivirus Infections |
| D018184 | Paramyxoviridae Infections |
| D018701 | Mononegavirales Infections |
| D012327 | RNA Virus Infections |
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| ID | Term |
|---|---|
| D008458 | Measles Vaccine |
| D022362 | Hepatitis A Vaccines |
| D019433 | Chickenpox Vaccine |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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Participants receive measles vaccine as part of routine medical care at 6 and 12 months of age. Half of the participants will receive varicella vaccine at 18 months of age and the other half will receive hepatitis-A at 18 months of age. All vaccines are administered according to their approved dosages, formulations and indications.
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| Hepatitis-A vaccine | Biological | Half of the participants (n=135) will receive hepatitis-A vaccine at 18 months of age. |
|
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| Varicella vaccine | Biological | Half of the participants (n=135) will receive varicella vaccine at 18 months of age. |
|
|
| Number of participants with seroprotective antibody titres (IgG ≥20 mIU/ml quantified by ELISA) one month post hepatitis-A vaccination |
Measured as seroprotection rate one month post hepatitis-A immunization in HIV-exposed (HEU, HIV-infected) and HIV-unexposed South African children. |
| 19 months of age (one month post vaccination) |
| Number of participants with vaccine-related adverse events after primary measles vaccination | Participants will be observed for at least 30 minutes after vaccination so that clinic personnel can observe and document any potential adverse reactions to the vaccine. Report of vaccine-related local (redness, swelling, pain/tenderness, itching) and systemic (fever, vomiting, poor appetite, irritability and decreased activity) adverse events will be solicited using diary card in the 7 days after vaccination. | 6 months of age |
| Number of participants with vaccine-related adverse events after booster measles vaccination | Participants will be observed for at least 30 minutes after vaccination so that clinic personnel can observe and document any potential adverse reactions to the vaccine. Report of vaccine-related local (redness, swelling, pain/tenderness, itching) and systemic (fever, vomiting, poor appetite, irritability and decreased activity) adverse events will be solicited using diary card in the 7 days after vaccination. | 12 months of age |
| Number of participants with vaccine-related adverse events after varicella vaccination | Participants will be observed for at least 30 minutes after vaccination so that clinic personnel can observe and document any potential adverse reactions to the vaccine. Report of vaccine-related local (redness, swelling, pain/tenderness, itching) and systemic (fever, vomiting, poor appetite, irritability and decreased activity) adverse events will be solicited using diary card in the 7 days after vaccination. | 18 months of age |
| Number of participants with vaccine-related adverse events after hepatitis-A vaccination | Participants will be observed for at least 30 minutes after vaccination so that clinic personnel can observe and document any potential adverse reactions to the vaccine. Report of vaccine-related local (redness, swelling, pain/tenderness, itching) and systemic (fever, vomiting, poor appetite, irritability and decreased activity) adverse events will be solicited using diary card in the 7 days after vaccination. | 18 months of age |
| Persistence of immunogenicity | Antibody concentrations and number of participants with seroprotective antibody levels to measles, varicella and hepatitis-A vaccination | 3, 4 and 5 years of age |
| Derived |
| Mutsaerts EAML, Nunes MC, Bhikha S, Ikulinda BT, Jose L, Koen A, Moultrie A, Grobbee DE, Klipstein-Grobusch K, Weinberg A, Madhi SA. Short-term immunogenicity and safety of hepatitis-A and varicella vaccines in HIV-exposed uninfected and HIV-unexposed South African children. Vaccine. 2020 May 8;38(22):3862-3868. doi: 10.1016/j.vaccine.2020.03.045. Epub 2020 Apr 16. |
| 31282539 | Derived | Mutsaerts EAML, Nunes MC, Bhikha S, Ikulinda BT, Boyce W, Jose L, Koen A, Moultrie A, Cutland CL, Grobbee DE, Klipstein-Grobusch K, Madhi SA. Immunogenicity and Safety of an Early Measles Vaccination Schedule at 6 and 12 Months of Age in Human Immunodeficiency Virus (HIV)-Unexposed and HIV-Exposed, Uninfected South African Children. J Infect Dis. 2019 Sep 26;220(9):1529-1538. doi: 10.1093/infdis/jiz348. |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D000073618 | Varicella Zoster Virus Infection |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D006525 | Hepatitis, Viral, Human |
| D004769 | Enterovirus Infections |
| D010850 | Picornaviridae Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D014761 |
| Viral Hepatitis Vaccines |
| D022283 | Herpesvirus Vaccines |