Influenza Vaccination of HIV Infected Pregnant Women: Safety and Immunogenicity

NCT01306682 | Completed Phase 2 DMC

• 1 other identifier: Maternal_flu_HIVpos_101107
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, placebo controlled trial will evaluate the safety and immunogenicity of Trivalent Influenza Vaccine (TIV) in HIV-infected pregnant women, dynamics of transplacental anti-influenza antibody transfer to their newborns and kinetics thereof during early infancy.

Conditions

Influenza

Outcome Measures

Primary Outcomes (2)

• Humoral immune responses to influenza strains in the vaccine will be measured to assess the immunogenicity of TIV in HIV-infected pregnant women vaccinated between 20-34 weeks of gestational age

  Humoral immunity will be measured by hemagglutination inhibition (HAI) assay. Blood will be collected at enrolment (pre-vaccination), one month post vaccination, delivery (+7 days) and 24 weeks post delivery. Humoral immune response definitions: HAI titers \< 1:10 = seronegative; ≥ 1:10 = seropositive; \> 1:40 = protected against influenza; Response to TIV = serconversion (from \<1:10 to ≥1:10) and/or 4-fold increase of HAI titers.

  1 month post vaccination, delivery (+7 days), 24 weeks post delivery

• The proportion of newborns born to HIV-infected mothers with hemagglutination inhibition (HAI) antibody titers of ≥1:40 to TIV strain will be determined and compared to newborns born to TIV-vaccinated HIV-uninfected women (parallel trial)

  Determine the proportion of newborns with hemagglutination inhibition (HAI) antibody titers of ≥1:40 to each of the three TIV strains born to HIV-infected mothers and compared to newborns born to TIV-vaccinated HIV-uninfected women

  Delivery (+7 days)

Secondary Outcomes (5)

• Hemagglutinin (HA) antibody measurements in blood taken from mother and infants up to 24 weeks post delivery will be used to assess dynamics and kinetics of transplacentally acquired antibodies

  24 weeks post partum

• The number of laboratory-confirmed or clinical influenza like illness cases in infants born to HIV infected mothers who received TIV or placebo will be used to determine efficacy of TIV vaccination of pregnant women against ILI in their infants

  24 weeks of age

• The number of laboratory-confirmed influenza illnesses and clinical ILI cases in maternal participants during pregnancy and for 24 weeks post-partum will be used to assess efficacy of TIV against laboratory confirmed and clinical ILI

  24 weeks

• Cell-mediated immune (CMI) responses to influenza strains in the vaccine will be measured to define CMI responses to TIV in HIV infected pregnant women

  1 month post vaccination

• CD4+ and HIV-viral load will be measured at baseline and one-month post vaccination to evaluate effect of TIV.

  1 month post vaccination

Study Arms (2)

Trivalent Influenza vaccine

ACTIVE COMPARATOR

0.5ml of TIV will be administered into deltoid muscle of non dominant arm

Biological: Trivalent influenza vaccine

Normal saline

PLACEBO COMPARATOR

0.5ml of normal saline administered into deltoid muscle of non dominant arm

Biological: Normal saline

Interventions

Trivalent influenza vaccine BIOLOGICAL

0.5 ml of trivalent influenza vaccine administered into deltoid muscle of non dominant arm

Also known as: Vaxigrip

Trivalent Influenza vaccine

Normal saline BIOLOGICAL

0.5ml normal saline administered into deltoid muscle of non dominant arm

Also known as: NaCl

Normal saline

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant women age \> 18 years to \< 39 years.
• Gestational age ≥ 20 weeks to \< 34 weeks documented by the approximate date of the last menstrual period and corroborated by physical exam.
• Documented to be HIV-infected on two assays prior to study-enrollment.
• Able to understand and comply with planned study procedures.
• Provides written informed consent prior to initiation of study.

You may not qualify if:

• In HIV-infected women features of WHO clinical category 3 or 4 of AIDS at the time of enrollment.
• Receipt of TIV, other than through the study, during the current influenza season documented by medical history or record.
• Receipt of any live licensed vaccine ≤ 28 days or inactivated licensed vaccine ≤ 14 days prior to study-vaccine.
• Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 28 days prior to vaccination in this study, or expects to receive another non-licensed agent before delivery unless study approval is obtained.
• Any significant (in the opinion of the site investigator) acute illness and/or oral temperature greater than or equal to 38 degrees C ≤ 24 hours prior to study entry.
• Use of anti-cancer systemic chemotherapy or radiation therapy ≤ 48 weeks of study enrollment, or has immunosuppression as a result of an underlying illness or treatment.
• Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) ≤ 12 weeks of study entry, or high-dose inhaled steroids (\> 800 mcg/day of beclomethasone dipropionate or equivalent) ≤ 12 weeks before study entry (nasal and topical steroids are allowed).
• Receipt of corticosteroids for preterm labor ≤ 14 days before study entry.(ix) Receipt of immunoglobulin or other blood products (with exception of Rho D immune globulin) ≤ 12 weeks prior to enrollment in this study or is scheduled to receive immunoglobulin or other blood products (with the exception of Rho D immune globulin) during pregnancy or for the first 24 weeks after delivery.
• Receipt of IL2, IFN, GMCSF or other immune mediators ≤ 12 weeks before enrollment.
• Uncontrolled major psychiatric disorder.
• History of a severe adverse reaction to previous TIV.
• Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
• Pregnancy complications (in the current pregnancy) such as pre-term labor, hypertension (systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mm Hg) or pre-eclampsia

Sponsors & Collaborators

• University of Witwatersrand, South Africa: lead
• Bill and Melinda Gates Foundation: collaborator
• Emory University: collaborator
• University of Colorado, Denver: collaborator

Study Sites (1)

RMPRU, Chris Hani Baragwanath Hospital

Soweto, Johannesburg, Gauteng, 2013, South Africa

Location

Related Publications (4)

• Motsoeneng BM, Dhar N, Nunes MC, Krammer F, Madhi SA, Moore PL, Richardson SI. Hemagglutinin Stalk-Specific Fc-Mediated Functions Are Associated With Protection Against Influenza Illness After Seasonal Influenza Vaccination. J Infect Dis. 2024 Dec 16;230(6):1329-1336. doi: 10.1093/infdis/jiae241.

  PMID: 38743692 DERIVED

• Madhi SA, Cutland CL, Downs S, Jones S, van Niekerk N, Simoes EAF, Nunes MC. Burden of Respiratory Syncytial Virus Infection in South African Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Pregnant and Postpartum Women: A Longitudinal Cohort Study. Clin Infect Dis. 2018 May 17;66(11):1658-1665. doi: 10.1093/cid/cix1088.

  PMID: 29253090 DERIVED

• Madhi SA, Nunes MC, Weinberg A, Kuwanda L, Hugo A, Jones S, van Niekerk N, Ortiz JR, Neuzil KM, Klugman KP, Simoes EAF, Cutland CL; Maternal Flu Trial (Matflu) Team. Contribution of Serologic Assays in the Evaluation of Influenza Virus Infection Rates and Vaccine Efficacy in Pregnant Women: Report From Randomized Controlled Trials. Clin Infect Dis. 2017 Jun 15;64(12):1773-1779. doi: 10.1093/cid/cix241.

  PMID: 28369198 DERIVED

• Madhi SA, Cutland CL, Kuwanda L, Weinberg A, Hugo A, Jones S, Adrian PV, van Niekerk N, Treurnicht F, Ortiz JR, Venter M, Violari A, Neuzil KM, Simoes EA, Klugman KP, Nunes MC; Maternal Flu Trial (Matflu) Team. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med. 2014 Sep 4;371(10):918-31. doi: 10.1056/NEJMoa1401480.

  PMID: 25184864 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; vaxigrip; Saline Solution

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Shabir A Madhi, MD, PhD

  University of Witwatersrand, South Africa

  STUDY CHAIR

• Keith P Klugman, MD, PhD

  Emory University

  STUDY DIRECTOR

• Adriana Weinberg, PhD

  University of Colorado, Denver

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical officer

Study Record Dates

• First Submitted: March 1, 2011
• First Posted: March 2, 2011
• Study Start: March 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: July 1, 2012
• Last Updated: February 7, 2013

Record last verified: 2013-02

Locations

ZA (1)