Safety of and Immune Response to an H1N1 Influenza Vaccine in HIV Infected Pregnant Women

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00992017
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 130
• Locations: 31
• Arm: 1
• Duration (Months): 13
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Both pregnant women and people infected with HIV are at increased risk of viral infection, including influenza infection. Pregnant women infected with HIV may be at particular risk of infection from the new H1N1 influenza virus. This study tested the safety and immunogenicity of an H1N1 influenza vaccine in pregnant women infected with HIV.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; H1N1 Influenza Virus	Biological: Influenza A (H1N1) monovalent vaccine	Phase 2

Detailed Description

On June 11, 2009, the World Health Organization declared a pandemic of the new H1N1 influenza virus, after the virus had caused significant fevers and respiratory illnesses in Mexico and the United States. Pregnant women are at an increased risk of complications from influenza. HIV infected people tend to have lower than normal antibody responses to seasonal influenza vaccines. Data suggest that larger than average doses of a vaccine counteract a weak antibody response. Preliminary results from ongoing studies of influenza A (H1N1) 2009 monovalent vaccines indicate that the vaccine may increase immune activation. This study tested the safety and antibody response of high doses of the influenza A (H1N1) 2009 monovalent vaccine in pregnant women infected with HIV.

Participation in this study lasted until 6 months after participants had delivered their babies or up to 52 weeks. Participants received two doses of the H1N1 vaccine at study entry and after 21 days. Each dose consisted of two intramuscular injections (four total injections). On the days of the injections, participants had their babies' heart rates checked before and after vaccination. At these visits, and at follow-up visits on Days 21, 31, and 42, participants completed a review of symptoms, physical and neurological exams, and a blood draw. For 10 days after receiving each dose of the vaccine, participants were asked to keep track of their temperatures and symptoms or reactions in a journal. Participants were contacted on Day 2 and Day 10 after the first dose of vaccine was given and on Day 2 after the second dose of vaccine was given. Some participants also received a phone call after 6 months.

At delivery of each participant's baby, blood was drawn from both the mother and umbilical cord (or from the baby if the cord blood could not be obtained). At 3 and 6 months after delivery, participants came in for follow-up visits involving, for both mother and child, a review of symptoms, brief physical exams, and blood draws (at 6 months only some women had a clinic visit, the rest received a phone call).

Study Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II Study to Assess the Safety and Immunogenicity of an Inactivated Monovalent Influenza A (H1N1) Vaccine in HIV-1 Infected Pregnant Women
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: H1N1 vaccine Pregnant women enrolled received two doses of H1N1 vaccine, administered 21 days apart.	Biological: Influenza A (H1N1) monovalent vaccine; Two 15-microgram intramuscular vaccine injections given together form one dose; two doses (four total injections) are given 21 days apart

Outcome Measures

Primary Outcome Measures

1. The Number of Participants Who Had at Least One Adverse Event (AE) [Measured up to 6 months after delivery]

   Shows the number of participants who had at least one adverse event (AE) in each category. These include: abnormal laboratory values, signs and symptoms, or diagnoses; solicited local AEs; and solicited systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

2. The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine [Measured up to 6 months after delivery]

   Shows the number of participants who experienced any events that were thought to be at least possibly related to study treatment. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

3. Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose [Measured at Day 21]

4. Percent of Pregnant Women With a Hemagglutination Inhibition (HAI) Titer of >= 40 [Measured at 21 days after first dose and at 10 days after second dose of study vaccine]

   Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.

Secondary Outcome Measures

1. Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery [Measured at delivery of the baby, and at 3 months and 6 months after delivery]

   Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.

2. Percent of Infants With an HAI Titer of >= 40 [Measured at birth (via cord blood) and at 3 months and 6 months of age]

   Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.

3. Maternal Geometric Mean Titers (GMT) of Antibodies HAI [Measured after the first and second doses of the vaccine, at delivery, and at 3 and 6 months after delivery]

   Presents the value of the geometric mean titer at each time point. Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.

4. Infant GMT of Antibodies HAI [Measured at birth and at 3 and 6 months of age]

   Presents the value of the geometric mean titer at each time point. Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.

5. Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values [Measured at entry, at 21 days after first dose of vaccine, at 10 days after second dose]

   The median and interquartile range (IQR) of B-Cell ELISPOT-measured IgG antibody-secreting cells (ASC)/10^6 PBMC and the median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 IFNgamma spot-forming cells (SFC)/10^6 PBMC.

6. Response to Seasonal Trivalent Influenza Vaccine (TIV) [Measured at entry]

   Presents the value of the median titer as well as the interquartile range at study entry. Antibodies to seasonal Influenza vaccine were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 39 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria for Step I:

• Confirmed diagnosis of HIV-1 infection

• Pregnant

• Between 14 and 35 weeks of gestation

• Documented platelet count of greater than 50,000 mm3 and an absolute neutrophil count (ANC) of greater than 500 mm3 within 28 days prior to study entry

• Able to understand and comply with planned study procedures

• On antiretroviral therapy (ART) as outlined in the treatment guidelines for pregnant HIV-1 infected women. Women must be currently taking ART or should initiate ART either prior to or concomitantly with the first dose of the vaccine.

Inclusion Criteria for Step II:

• Received the first dose of influenza A (H1N1) 2009 monovalent vaccine

• Has a documented platelet count of greater than 50,000 mm3 and an ANC of greater than 500 mm3 within the 28 days prior to Step II entry

Exclusion Criteria for Step I:

• Has a known allergy to eggs, egg products, neomycin, or polymyxin

• Has a history, in the opinion of the site investigator, of severe reactions following previous immunization with seasonal TIV

• Participation in a novel H1N1 influenza vaccine study in the past 2 years

• Proven history, by reverse transcription polymerase chain reaction (RT-PCR), of novel influenza H1N1 infection or positive influenza diagnostic test since June 2009 (specificity to H1N1 not required) prior to study entry

• Received any other live licensed vaccine within 4 weeks or inactivated licensed vaccine within 2 weeks prior to study entry

• Received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or medication) within 4 weeks prior to vaccination in this study or expects to receive another nonlicensed agent before delivery

• Acute illness and/or an oral temperature greater than or equal to 100.0 degrees F within 24 hours prior to study entry

• Use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months of study enrollment or has immunosuppression as a result of an underlying illness or treatment (other than HIV-1 infection)

• Active neoplastic disease (excluding nonmelanoma skin cancer, human papillomavirus [HPV]-related cervical dysplasia, and cervical intraepithelial neoplasia [CIN] Grades 1, 2, or 3)

• Long-term use of glucocorticoids, including oral or parenteral prednisone or equivalent (at least 2.0 mg/kg per day or at least 20 mg total dose) for more than 2 consecutive weeks (or 2 weeks total) in the past 3 months or high-dose inhaled steroids (more than 800 mcg/day of beclomethasone dipropionate or equivalent) within the past 3 months. Nasal and topical steroids are allowed.

• Received immunoglobulin or other blood products (with exception of Rho D immune globulin) within the 3 months prior to enrollment in this study

• Current diagnosis of uncontrolled major psychiatric disorder

• History of Guillain-Barre syndrome in the subject or subject's family (including parents, siblings, half-siblings, or children)

• Onset of a neurological disorder including (but not limited to) absent ankle and patellar deep tendon reflexes (DTRs) in both legs (all four absent) within the past 6 months

• Disproportionate loss of strength in lower extremity or extremities compared to the upper extremities (not thought to be related to pregnancy) within the past 6 months

• 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 such as preterm labor, hypertension and pre-eclampsia are not exclusion criteria for this study.

Exclusion Criteria for Step II:

• Received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or medication), other than from participation in this study, since the study vaccine dose #1 or expects to receive another nonlicensed agent before delivery

• Use of anti-cancer chemotherapy or radiation therapy since study vaccine dose #1, new diagnosis of an active malignancy, or is immunosuppressed as a result of an underlying illness (other than HIV-1 infection) or treatment

• Use of glucocorticoids, including oral or parenteral prednisone or equivalent (at least 2.0 mg/kg per day or at least 20 mg total dose) or high-dose inhaled steroids (more than 800 mcg/day of beclomethasone dipropionate or equivalent) for more than 2 consecutive weeks (or 2 weeks total) since study vaccine dose #1. Nasal and topical steroids are allowed.

• Received immunoglobulin or other blood products (with exception of Rho D immune globulin) since study vaccine dose #1

• A new diagnosis of uncontrolled major psychiatric disorder since study vaccine dose #1

• New occurrence or new awareness of Guillain-Barre syndrome in the subject or subject's family (including parents, siblings, half-siblings, or children) since study vaccine dose #1

• A new onset of a neurological disorder including (but not limited to) absent ankle and patellar DTRs in both legs (all four absent) since study vaccine dose #1

• Disproportionate loss of strength in lower extremity or extremities compared to the upper extremities (not thought to be related to pregnancy) since study vaccine dose #1

• Any Grade 3 toxicity or AE experienced by a participant unless the investigator has received protocol team approval

• Any Grade 4 toxicity or AE (other than injection site reaction or fever) that is definitely, probably, or possibly related to the study vaccine dose #1

• Any Grade 4 injection site reactions or fever experienced by a subject, unless the investigator has received protocol team approval

• Any Grade 4 AEs that are definitely not or probably not related to study vaccine, unless the investigator has received protocol team approval

• Any new clinical findings since the study vaccine dose #1, that, in the investigator's opinion, would compromise the safety of the participant

• Participant refuses further vaccination. The subject will still be asked to complete safety visits and be followed in the study.

• Participant withdraws consent. Participants may withdraw their consent for study participation at any time and for any reason, without penalty.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Usc La Nichd Crs	Alhambra	California	United States	91803
2	University of California, UC San Diego CRS	La Jolla	California	United States	92093-0672
3	Miller Children's Hosp. Long Beach CA NICHD CRS	Long Beach	California	United States	90806
4	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California	United States	90095-1752
5	Univ. of California San Francisco NICHD CRS	San Francisco	California	United States	94143
6	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado	United States	80045
7	Washington Hosp. Ctr. NICHD CRS	Washington	District of Columbia	United States	20010
8	South Florida CDTC Ft Lauderdale NICHD CRS	Fort Lauderdale	Florida	United States	33316
9	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida	United States	32209
10	Pediatric Perinatal HIV Clinical Trials Unit CRS	Miami	Florida	United States	33136
11	USF - Tampa NICHD CRS	Tampa	Florida	United States	33606
12	Rush Univ. Cook County Hosp. Chicago NICHD CRS	Chicago	Illinois	United States	60612
13	Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS	Chicago	Illinois	United States	60614-3393
14	Tulane Univ. New Orleans NICHD CRS	New Orleans	Louisiana	United States	70112
15	Johns Hopkins Univ. Baltimore NICHD CRS	Baltimore	Maryland	United States	21287
16	Children's Hosp. of Boston NICHD CRS	Boston	Massachusetts	United States	02115
17	Boston Medical Center Ped. HIV Program NICHD CRS	Boston	Massachusetts	United States	02118
18	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts	United States	01605
19	Rutgers - New Jersey Medical School CRS	Newark	New Jersey	United States	07103
20	Bronx-Lebanon CRS	Bronx	New York	United States	10457
21	Jacobi Med. Ctr. Bronx NICHD CRS	Bronx	New York	United States	10461
22	Metropolitan Hosp. NICHD CRS	New York	New York	United States	10029
23	Columbia IMPAACT CRS	New York	New York	United States	10032
24	SUNY Stony Brook NICHD CRS	Stony Brook	New York	United States	11794-8111
25	DUMC Ped. CRS	Durham	North Carolina	United States	27710
26	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania	United States	19104
27	St. Jude Children's Research Hospital CRS	Memphis	Tennessee	United States	38105-3678
28	Texas Children's Hospital CRS	Houston	Texas	United States	77030-2399
29	Seattle Children's Research Institute CRS	Seattle	Washington	United States	98101
30	University of Puerto Rico Pediatric HIV/AIDS Research Program CRS	San Juan		Puerto Rico	00935
31	San Juan City Hosp. PR NICHD CRS	San Juan		Puerto Rico	00936

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Study Chair: Sharon Nachman, MD, State University of New York at Stony Brook

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for information on the IMPAACT group and for the package insert on the H1N1 vaccine.
• Click here for updated results from clinical trials regarding H1N1 influenza.
• Click here for the table used for grading toxicities: DAIDS Grading Severity of AEs, V1.0, Dec04

Publications

• Jamieson DJ, Honein MA, Rasmussen SA, Williams JL, Swerdlow DL, Biggerstaff MS, Lindstrom S, Louie JK, Christ CM, Bohm SR, Fonseca VP, Ritger KA, Kuhles DJ, Eggers P, Bruce H, Davidson HA, Lutterloh E, Harris ML, Burke C, Cocoros N, Finelli L, MacFarlane KF, Shu B, Olsen SJ; Novel Influenza A (H1N1) Pregnancy Working Group. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet. 2009 Aug 8;374(9688):451-8. doi: 10.1016/S0140-6736(09)61304-0. Epub 2009 Jul 28.
• Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009 Jun 18;360(25):2605-15. doi: 10.1056/NEJMoa0903810. Epub 2009 May 7. Erratum in: N Engl J Med. 2009 Jul 2;361(1):102.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00992017
• Other Study ID Numbers: P1086; 10835; IMPAACT P1086
• First Posted: Oct 8, 2009
• Last Update Posted: Nov 5, 2021
• Last Verified: Dec 1, 2014

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Vaccine; Pregnant; Perinatal
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Pregnant women were enrolled from 31 sites between October 8, 2009 and November 13, 2009.
Pre-assignment Detail	Two study participants were enrolled but left the clinic before receiving any vaccination and they were taken off study.

Arm/Group Title	H1N1 Vaccine
Arm/Group Description	Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Period Title: Overall Study
STARTED	128
Received Both Study Vaccinations	124
Received Only One Study Vaccination	4
COMPLETED	118
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	H1N1 Vaccine
Arm/Group Description	Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Overall Participants	128
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28 (6)
Sex: Female, Male (Count of Participants)
Female	128 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	112 87.5%
Puerto Rico	16 12.5%
CD4 Cells Count (cells / mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells / mm^3]	504 (264)
Percentage of CD4 Cells (percentage of CD4 cells) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of CD4 cells]	30 (11)
Gestational Age (Weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Weeks]	25 (6)

Outcome Measures

1. Primary Outcome

Title	The Number of Participants Who Had at Least One Adverse Event (AE)
Description	Shows the number of participants who had at least one adverse event (AE) in each category. These include: abnormal laboratory values, signs and symptoms, or diagnoses; solicited local AEs; and solicited systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Time Frame	Measured up to 6 months after delivery

Outcome Measure Data

Analysis Population Description

All 128 pregnant women who received at least one vaccination are included in this analysis.

Arm/Group Title	H1N1 Vaccine
Arm/Group Description	Pregnant women enrolled in the study.
Measure Participants	128
Overall (New AEs after start of treatment)	118 92.2%
Grade 4 AEs (New, after start of treatment)	11 8.6%
Grade 3 AEs (New, after start of treatment)	8 6.3%
Grade >=2 local and systemic AEs to injection	0 0%

2. Primary Outcome

Title	The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine
Description	Shows the number of participants who experienced any events that were thought to be at least possibly related to study treatment. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Time Frame	Measured up to 6 months after delivery

Outcome Measure Data

Analysis Population Description

All 128 pregnant women who received at least one vaccination are included.

Arm/Group Title	Vaccinated Study Participants
Arm/Group Description	Pregnant women who received at least one H1N1 vaccination.
Measure Participants	128
Number [Participants]	0 0%

3. Primary Outcome

Title	Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose
Time Frame	Measured at Day 21

Outcome Measure Data

Analysis Population Description

All 128 pregnant women who received at least one vaccination are included.

Arm/Group Title	Vaccinated Study Participants
Arm/Group Description	Pregnant women who received at least one H1N1 vaccination.
Measure Participants	128
Number [Participants]	0 0%

4. Primary Outcome

Title	Percent of Pregnant Women With a Hemagglutination Inhibition (HAI) Titer of >= 40
Description	Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.
Time Frame	Measured at 21 days after first dose and at 10 days after second dose of study vaccine

Outcome Measure Data

Analysis Population Description

The analysis population consists of the eligible pregnant women with nonmissing HAI titers, who had not delivered prior to the evaluation, and had received all doses of vaccine up to that timepoint. The N for the analyses of HAI titers after the first and second vaccinations were 118 and 108, respectively.

Arm/Group Title	H1N1 Vaccine
Arm/Group Description	The pregnant women who received the H1N1 vaccinations.
Measure Participants	118
Percent with titers >= 40 post dose 1 (N=118)	73.7 57.6%
Percent with titers >= 40 post dose 2 (N=108)	80.6 63%

5. Secondary Outcome

Title	Percent of Pregnant Women With an HAI Titer of >= 40 at Delivery, 3 Months and 6 Months After Delivery
Description	Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.
Time Frame	Measured at delivery of the baby, and at 3 months and 6 months after delivery

Outcome Measure Data

Analysis Population Description

The population consists of eligible pregnant women with nonmissing HAI titers, who had not delivered before the evaluation post second dose, and received two doses of vaccine. The N for the analyses of HAI titers at delivery, and at 3 and 6 months after were 102, 92 and 58, respectively. Only some women had a clinic visit at 6 months post delivery.

Arm/Group Title	H1N1 Vaccine
Arm/Group Description	Pregnant women who received H1N1 vaccinations.
Measure Participants	102
% with titers >= 1:40 at delivery (N=102)	65.7 51.3%
% with titers >= 1:40 at 3 mo post delivery (N=92)	55.4 43.3%
% with titers >= 1:40 at 6 mo post delivery (N=58)	60.3 47.1%

6. Secondary Outcome

Title	Percent of Infants With an HAI Titer of >= 40
Description	Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.
Time Frame	Measured at birth (via cord blood) and at 3 months and 6 months of age

Outcome Measure Data

Analysis Population Description

The population consists of infants born to eligible women with nonmissing HAI titers, who had not delivered before the evaluation post second dose, and received two doses of vaccine. The N for analyses at birth, 3 and 6 months were 96, 87 and 52, respectively. Cord blood was used when available. Only some infants had a clinic visit at 6 months.

Arm/Group Title	Infants
Arm/Group Description	Infants born to pregnant women who received H1N1 vaccines.
Measure Participants	96
% infants with titers >= 1:40 at birth (N=96)	64.6 50.5%
% infants with titers >= 1:40 at 3 months (N=87)	23.0 18%
% infants with titers >= 1:40 at 6 months (N=52)	11.5 9%

7. Secondary Outcome

Title	Maternal Geometric Mean Titers (GMT) of Antibodies HAI
Description	Presents the value of the geometric mean titer at each time point. Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.
Time Frame	Measured after the first and second doses of the vaccine, at delivery, and at 3 and 6 months after delivery

Outcome Measure Data

Analysis Population Description

The population consists of eligible women with nonmissing HAI titers, who had not delivered before the evaluation post first or second dose, and received all vaccines up to that point, respectively. The N for analyses after the first and second vaccinations, at delivery, 3 and 6 months after were 104, 94, 102, 92 and 58, respectively.

Arm/Group Title	H1N1 Vaccine
Arm/Group Description	Pregnant women who received the H1N1 vaccines.
Measure Participants	104
Post first vaccination (N=104)	83
Post second vaccination (N=94)	81
At delivery (N=102)	50
At 3 months post delivery (N=92)	36
At 6 months post delivery (N=58)	38

8. Secondary Outcome

Title	Infant GMT of Antibodies HAI
Description	Presents the value of the geometric mean titer at each time point. Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.
Time Frame	Measured at birth and at 3 and 6 months of age

Outcome Measure Data

Analysis Population Description

The population consists of infants born to eligible women with nonmissing HAI titers, who had not delivered before the evaluation post second dose, and received two doses of vaccine. The N for analyses at birth, 3 and 6 months were 96, 87 and 52, respectively. Cord blood was used when available. Only some infants had a clinic visit at 6 months.

Arm/Group Title	Infants
Arm/Group Description	Infants born to pregnant women who received H1N1 vaccines.
Measure Participants	96
At birth (N=96 infants)	56
At 3 months (N=87 infants)	13
At 6 months (N=52 infants)	14

9. Secondary Outcome

Title	Maternal Cell-mediated Immunity (CMI) Responses, as Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values
Description	The median and interquartile range (IQR) of B-Cell ELISPOT-measured IgG antibody-secreting cells (ASC)/10^6 PBMC and the median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 IFNgamma spot-forming cells (SFC)/10^6 PBMC.
Time Frame	Measured at entry, at 21 days after first dose of vaccine, at 10 days after second dose

Outcome Measure Data

Analysis Population Description

The pregnant women who had not delivered prior to the evaluation, had received all doses of vaccine up to that timepoint and had sufficient samples for testing.

Arm/Group Title	H1N1 Vaccine
Arm/Group Description	The pregnant women who received the H1N1 vaccinations.
Measure Participants	45
IgG ASC/10^6 PBMC, Week 0 (N=36)	6
IgG ASC/10^6 PBMC, Post Dose 1 (N=36)	15
IgG ASC/10^6 PBMC, Post Dose 2 (N=39)	14
pH1N1 IFNgamma SFC/10^6 PBMC, Week 0 (N=45)	166
pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 1 (N=44)	117
pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 2 (N=43)	76

10. Secondary Outcome

Title	Response to Seasonal Trivalent Influenza Vaccine (TIV)
Description	Presents the value of the median titer as well as the interquartile range at study entry. Antibodies to seasonal Influenza vaccine were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.
Time Frame	Measured at entry

Outcome Measure Data

Analysis Population Description

Pregnant women who received the first H1N1 immunization.

Arm/Group Title	H1N1 Vaccine
Arm/Group Description	Pregnant women who received the H1N1 vaccines.
Measure Participants	128
Median (Inter-Quartile Range) [titer]	20

Adverse Events

Time Frame	Adverse events were collected from the date of enrollment in the study until 6 months after delivery.
Adverse Event Reporting Description	Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Arm/Group Title	H1N1 Vaccine
Arm/Group Description	Pregnant women received two doses of H1N1 vaccine administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
All Cause Mortality
	H1N1 Vaccine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	H1N1 Vaccine
	Affected / at Risk (%)	# Events
Total	21/128 (16.4%)
Gastrointestinal disorders
Vomiting	1/128 (0.8%)
General disorders
Influenza like illness	1/128 (0.8%)
Infections and infestations
Pneumonia	1/128 (0.8%)
Wound infection	1/128 (0.8%)
Injury, poisoning and procedural complications
Wound dehiscence	1/128 (0.8%)
Musculoskeletal and connective tissue disorders
Flank pain	1/128 (0.8%)
Nervous system disorders
Hypoaesthesia	1/128 (0.8%)
Paraesthesia	1/128 (0.8%)
VIIth nerve paralysis	1/128 (0.8%)
Pregnancy, puerperium and perinatal conditions
Complication of pregnancy	1/128 (0.8%)
Intra-uterine death	1/128 (0.8%)
Placenta accreta	1/128 (0.8%)
Pre-eclampsia	5/128 (3.9%)
Premature labour	3/128 (2.3%)
Premature rupture of membranes	1/128 (0.8%)
Psychiatric disorders
Conversion disorder	1/128 (0.8%)
Vascular disorders
Deep vein thrombosis	1/128 (0.8%)
Other (Not Including Serious) Adverse Events
	H1N1 Vaccine
	Affected / at Risk (%)	# Events
Total	118/128 (92.2%)
Blood and lymphatic system disorders
Iron deficiency anaemia	9/128 (7%)
Gastrointestinal disorders
Abdominal pain	12/128 (9.4%)
Diarrhoea	11/128 (8.6%)
Nausea	24/128 (18.8%)
Vomiting	15/128 (11.7%)
General disorders
Fatigue	9/128 (7%)
Pyrexia	8/128 (6.3%)
Infections and infestations
Bacterial disease carrier	7/128 (5.5%)
Vaginitis bacterial	8/128 (6.3%)
Vulvovaginal candidiasis	16/128 (12.5%)
Investigations
Alanine aminotransferase increased	10/128 (7.8%)
Aspartate aminotransferase increased	8/128 (6.3%)
Blood albumin abnormal	30/128 (23.4%)
Blood alkaline phosphatase increased	7/128 (5.5%)
Blood bicarbonate abnormal	14/128 (10.9%)
Blood glucose decreased	16/128 (12.5%)
Blood sodium decreased	25/128 (19.5%)
Haemoglobin decreased	21/128 (16.4%)
Musculoskeletal and connective tissue disorders
Back pain	11/128 (8.6%)
Pain in extremity	11/128 (8.6%)
Nervous system disorders
Dizziness	9/128 (7%)
Headache	31/128 (24.2%)
Pregnancy, puerperium and perinatal conditions
Pre-eclampsia	7/128 (5.5%)
Reproductive system and breast disorders
Vaginal discharge	19/128 (14.8%)
Vaginal haemorrhage	9/128 (7%)
Vulvovaginal pruritus	11/128 (8.6%)
Respiratory, thoracic and mediastinal disorders
Cough	22/128 (17.2%)
Nasal congestion	18/128 (14.1%)
Oropharyngeal pain	11/128 (8.6%)
Skin and subcutaneous tissue disorders
Rash	7/128 (5.5%)
Vascular disorders
Hypertension	11/128 (8.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.