In the Journals

Influenza vaccination strategy for pregnant women with HIV still needs improvement

A double-dose influenza vaccine regimen resulted in slightly greater immunogenicity among pregnant women with HIV than a single-dose regimen, although immunogenicity among women who received the double dose was still lower than historical data from women without HIV in the same setting, according to findings published in The Lancet.

“Four randomized clinical trials have shown that vaccination of pregnant women against influenza reduces the risk of influenza illness in their infants during the first 6 months of life. However, the only trial that assessed vaccine efficacy among infants born to women living with HIV in South Africa did not detect a protective effect in this group . . . ,” the authors wrote. “We found only one study that described immunogenicity in pregnant women with HIV and the antibody levels of their infants after two doses of inactivated A/H1N1/2009 pandemic monovalent vaccine (two doses of 30 g) during pregnancy. That study reported that a two-dose regimen was moderately immunogenic and that seroprotective titers were present in 67% of mothers and 65% of infants at delivery. After the second dose, only a slight improvement in seroprotection was seen.”

Marta C. Nunes, PhD, a senior scientist at the Respiratory and Meningeal Pathogens Research Unit at the Chris Hani Baragwanath Hospital in South Africa, and colleagues aimed to determine whether raising the vaccine antigen content or giving a second dose of the vaccine would heighten the immunogenicity of the trivalent inactivated influenza vaccine among pregnant women with HIV and the protection of their infants against the illness compared with a single, standard dose.

The researchers performed a double-blind, randomized controlled trial with pregnant women who also had HIV from seven antenatal clinics in Soweto, South Africa. Women with HIV were eligible for the study if they were aged between 18 and 38 years and had an estimated gestational age of 12 to 36 weeks.

Patients were randomly assigned 1:1:1 via a computer-generated randomization list to receive 15 µg of three seasonal strains of influenza as a single dose, a double dose or two single doses 1 month apart.

Hemagglutination-inhibition antibody responses were assessed at enrollment and at 1 month after each dose of vaccine; these responses were also assessed within 7 days of birth in the single- and double-dose groups, Nunes and colleagues wrote. Immunogenicity analyses were done only among women with visits 28 to 35 days apart and infants who were born at least 28 days after maternal immunization.

The primary outcome was the seroconversion rate to each of the vaccine strains 1 month after the dosing schedule was finished.

The primary safety outcomes were frequency of local and systematic reactions. Safety was evaluated in mothers and infants until 24 weeks’ postpartum in all patients who received at least one dose of the vaccine.

Of the 800 women enrolled in the trial, 266 were placed in the single-dose group; there were 265 women in the double-dose group and 269 in the two single-doses group.

Seroconversion rates in mothers 1 month after the final vaccine was administered were higher in the double-dose group (n = 230; range, 29% to 65% for the three vaccine strains) compared with the single-dose group (n = 230; range, 18% to 49%; P .019 for the three vaccine strains). Seroconversion rates were similar between the group receiving two single doses of the vaccine (n = 220; range, 23% to 52%) and the single-dose group.

Safety outcomes were comparable between the three groups, although participants in the double-dose group did experience more injection-site reactions.

“These findings emphasize the need for continued efforts to find an improved influenza vaccine or vaccination strategy for this population to improve protection of their infants, such as exploring the use of high-dose inactivated influenza vaccine that is currently approved for older adults,” the researchers wrote.

In an accompanying editorial, Sharon Nachman, MD, chief of the division of pediatric infectious diseases, director of the clinical trials office and professor of pediatrics at Stony Brook University, wrote that, although the study by Nunes and colleagues had “many successes,” the “best vaccine” for use in this population has yet to be identified.

“Pregnancy is a time of immune compromise and the prevention of illness should be at the forefront of care,” Nachman wrote. “The lack of understanding [about] how to use products, both in the pipeline and those licensed but with no data for use in pregnancy, handicaps our ability to provide optimal care to out pregnant patients and their infants. We should aim to protect pregnant women through research rather than from research and Nunes and colleagues should be commended for trying to do so.” – by Earl Holland Jr.

Disclosures: Nunes reports receiving grant support from MedImmune and honoraria from Pfizer and Sanofi Pasteur outside of the submitted work. Nachman reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

A double-dose influenza vaccine regimen resulted in slightly greater immunogenicity among pregnant women with HIV than a single-dose regimen, although immunogenicity among women who received the double dose was still lower than historical data from women without HIV in the same setting, according to findings published in The Lancet.

“Four randomized clinical trials have shown that vaccination of pregnant women against influenza reduces the risk of influenza illness in their infants during the first 6 months of life. However, the only trial that assessed vaccine efficacy among infants born to women living with HIV in South Africa did not detect a protective effect in this group . . . ,” the authors wrote. “We found only one study that described immunogenicity in pregnant women with HIV and the antibody levels of their infants after two doses of inactivated A/H1N1/2009 pandemic monovalent vaccine (two doses of 30 g) during pregnancy. That study reported that a two-dose regimen was moderately immunogenic and that seroprotective titers were present in 67% of mothers and 65% of infants at delivery. After the second dose, only a slight improvement in seroprotection was seen.”

Marta C. Nunes, PhD, a senior scientist at the Respiratory and Meningeal Pathogens Research Unit at the Chris Hani Baragwanath Hospital in South Africa, and colleagues aimed to determine whether raising the vaccine antigen content or giving a second dose of the vaccine would heighten the immunogenicity of the trivalent inactivated influenza vaccine among pregnant women with HIV and the protection of their infants against the illness compared with a single, standard dose.

The researchers performed a double-blind, randomized controlled trial with pregnant women who also had HIV from seven antenatal clinics in Soweto, South Africa. Women with HIV were eligible for the study if they were aged between 18 and 38 years and had an estimated gestational age of 12 to 36 weeks.

Patients were randomly assigned 1:1:1 via a computer-generated randomization list to receive 15 µg of three seasonal strains of influenza as a single dose, a double dose or two single doses 1 month apart.

Hemagglutination-inhibition antibody responses were assessed at enrollment and at 1 month after each dose of vaccine; these responses were also assessed within 7 days of birth in the single- and double-dose groups, Nunes and colleagues wrote. Immunogenicity analyses were done only among women with visits 28 to 35 days apart and infants who were born at least 28 days after maternal immunization.

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The primary outcome was the seroconversion rate to each of the vaccine strains 1 month after the dosing schedule was finished.

The primary safety outcomes were frequency of local and systematic reactions. Safety was evaluated in mothers and infants until 24 weeks’ postpartum in all patients who received at least one dose of the vaccine.

Of the 800 women enrolled in the trial, 266 were placed in the single-dose group; there were 265 women in the double-dose group and 269 in the two single-doses group.

Seroconversion rates in mothers 1 month after the final vaccine was administered were higher in the double-dose group (n = 230; range, 29% to 65% for the three vaccine strains) compared with the single-dose group (n = 230; range, 18% to 49%; P .019 for the three vaccine strains). Seroconversion rates were similar between the group receiving two single doses of the vaccine (n = 220; range, 23% to 52%) and the single-dose group.

Safety outcomes were comparable between the three groups, although participants in the double-dose group did experience more injection-site reactions.

“These findings emphasize the need for continued efforts to find an improved influenza vaccine or vaccination strategy for this population to improve protection of their infants, such as exploring the use of high-dose inactivated influenza vaccine that is currently approved for older adults,” the researchers wrote.

In an accompanying editorial, Sharon Nachman, MD, chief of the division of pediatric infectious diseases, director of the clinical trials office and professor of pediatrics at Stony Brook University, wrote that, although the study by Nunes and colleagues had “many successes,” the “best vaccine” for use in this population has yet to be identified.

“Pregnancy is a time of immune compromise and the prevention of illness should be at the forefront of care,” Nachman wrote. “The lack of understanding [about] how to use products, both in the pipeline and those licensed but with no data for use in pregnancy, handicaps our ability to provide optimal care to out pregnant patients and their infants. We should aim to protect pregnant women through research rather than from research and Nunes and colleagues should be commended for trying to do so.” – by Earl Holland Jr.

Disclosures: Nunes reports receiving grant support from MedImmune and honoraria from Pfizer and Sanofi Pasteur outside of the submitted work. Nachman reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.