Vaccination of HIV-infected pregnant women: implications for protection of their young infants
© The Author(s). 2017
Received: 9 November 2016
Accepted: 18 December 2016
Published: 6 January 2017
The prevention of mother to child transmission of HIV has resulted in reduced burden of pediatric HIV-infection, but the prevalence of maternal HIV infection remains high in sub-Saharan African countries. HIV-exposed-uninfected infants have an increased risk of morbidity and mortality due to infectious diseases than HIV-unexposed infants, particularly during the first six months of life, which in part might be due to lower levels of pathogen-specific protective antibodies acquired transplacentally from their mothers. This could be mitigated by vaccinating pregnant women to boost antibody levels; although vaccine responses among HIV-infected pregnant women might differ compared to HIV-uninfected women. We reviewed studies that compared natural and vaccine-induced antibody levels to different epitopes between HIV-infected and HIV-uninfected pregnant women.
Most studies reported lower baseline/pre-vaccination antibody levels in HIV-infected pregnant women, which may not be reversed by antiretroviral therapy during pregnancy. There were only few studies on vaccination of HIV-infected pregnant women, mainly on influenza virus and group B Streptococcus (GBS) vaccines. Immunogenicity studies on influenza vaccines indicated that HIV-infected pregnant women had lower vaccine induced hemagglutination inhibition antibody titers and a decreased likelihood of seroconversion compared to HIV-uninfected women; and while higher CD4+ T-lymphocyte levels were associated with better immune responses to vaccination, HIV viral load was not associated with responses. Furthermore, infants born to influenza vaccinated HIV-infected pregnant women also had lower antibody levels and a lower proportion of HIV-exposed infants had titers above the putative correlate of protection compared to HIV-unexposed infants. The immunogenicity of a CRM197-conjugated trivalent GBS vaccine was also lower in HIV-infected pregnant women compared to HIV-uninfected women, irrespective of CD4+ T-lymphocyte counts.
Poorer immunogenicity of vaccines reported in HIV-infected compared to HIV-uninfected pregnant women might compromise the potential benefits to their young infants. Alternate vaccination strategies, including vaccines with higher antigen concentration, adjuvanted vaccines or multiple doses schedules might be required in HIV-infected pregnant women to optimize antibody transferred to their fetuses.
KeywordsPregnant women HIV Antibody Immunity Vaccine
HIV-exposed infants, a new vulnerable population
Incidence ratio ratio’s and mortality in HIV-exposed and –unexposed infants less than 6 months of age
Incidence (95% CI) per 100 000
Incidence rate ratio (95% CI)
Streptococcus pneumoniae 
Streptococcus agalactiae b 
Lower respiratory tract associated hospitalization
Respiratory syncytial virus 
Human metapneumovirus 
The possible mechanisms for the increased susceptibility of HEU infants to infectious diseases were recently reviewed [3, 4, 10]. This included lower levels of pathogen-specific protective antibodies among HIV-infected women and reduced efficiency of transplacental transfer of antibodies. The lower epitope-specific antibody concentrations against vaccine preventable diseases in HIV-infected women [11–13], is likely due to HIV-induced loss of memory T- and B-lymphocyte function. Furthermore, placental abnormalities and saturation of active transport receptors may also result in inefficient transplacental antibody transfer to fetuses of HIV-infected women . Compounding this might be immune dysregulation such as T-cell activation, increased pro-inflammatory cytokines secretion, and increased lymphocyte apoptosis in HEU infants . Reduced thymic sizes and lower CD4+ T-lymphocyte counts were also observed in HEU infants. Although not clearly understood, in-utero antiretroviral therapy (ART) exposure has been associated with mitochondrial toxicity, lower numbers of circulating T-cell lymphocytes and neutrophils in young infants .
Maternal vaccination as a strategy to prevent infant disease
Vaccination during pregnancy could potentially improve maternal and child health , as already shown by the effectiveness of vaccination during pregnancy with tetanus toxoid vaccine in reducing mortality from neonatal tetanus in low-middle income countries by >80% from proximately 1.27 million cases in the 1980s to <50,000 cases by 2013 . Also, in the USA and some European countries, maternal vaccination strategies have been adopted for the prevention of influenza and pertussis in the women and their young infants . There is growing public awareness about the benefits of maternal vaccination; with 72% of women in the United Kingdom considering vaccination during pregnancy as acceptable .
The protection of the infants could either be due to prevention of mother-to-child transmission of pathogens during close contact, or through transfer of maternal epitope-specific protective antibodies via the placenta and/or breastmilk. This is especially beneficial against diseases presenting soon after birth, or during the initial vulnerable period prior to young infants completing their immunization against vaccine preventable diseases . The effectiveness of vaccination of pregnant women in protecting their infants through transplacental antibody transfer depends on a number of factors such as: (i) the immunogenicity of the vaccine among pregnant women, (ii) baseline maternal antibody levels and underlying prevalence of memory lymphocytes, (iii) subclass of the antibodies induced by the vaccine, (iv) efficiency of transplacental antibody transfer, (v) adequate gestational time to allow for optimal in-utero transplacental transfer of antibodies, and (vi) antibody half-life in the women and infant .
The transplacental acquired antibodies in the fetus are almost exclusively IgG antibodies, with more efficient and abundant transfer of IgG1 compared to IgG2 . IgG2 is preferentially induced by polysaccharide epitopes, used in many vaccines against encapsulated organisms such as Streptococcus pneumoniae, GBS and Haemophilus influenzae type b; whereas IgG1 is induced primarily by protein epitopes [14, 18]. The transfer of maternal antibodies across the placenta is via an active transport mechanism utilizing Fc receptors . To transfer from the maternal to the fetal circulation, IgG need to cross over the syncytiotrophoblast and the fetal endothelium . Factors that might influence this transplacental antibody transfer include placental integrity, the IgG subclass, maternal nutritional status, parity/gravidity and gestational age [11, 14, 21].
Vaccination during pregnancy aimed at protecting the infants, needs to induce sufficient maternal antibody levels that will be transferred to the fetus within the remaining gestational period; and persist in the infant through early infancy. The active transfer of maternal IgG antibodies (natural or vaccine-induced) occurs most efficiently in the third trimester of pregnancy . Infant to maternal antibody ratios are variable for different antigens, estimates generally range between 75 to 135% at term (≥37 weeks), 50–95% at 33–36 weeks, and 30–55% at 28–32 weeks gestation age [22–24]. Although a more efficient transfer of antibodies occurs in the last weeks before birth, infants born to women vaccinated in the second trimester had higher levels of pertussis antibodies than those vaccinated in the third trimester . Generally, maternal and cord blood antibody concentrations are correlated; though higher maternal antibody concentrations and more efficient transplacental transfer are noted in mothers in high-income countries compared to low-income countries [11, 26]. This difference is most probably attributable to the higher prevalence of chronic maternal infections, placental infections or undernutrition in low-income countries [11, 27].
Maternal HIV-infection and vaccination
This could be further compounded by reduced transplacental antibody transfer in HIV-infected compared to HIV–uninfected mother-newborn dyads (Fig. 1). HIV-infection is associated with a hyper-gammaglobulinemia state which might result in saturation of the Fc receptors, hence impeding antibody transfer to the fetus . Studies have reported lower newborn to maternal antibody ratios for measles, varicella, tetanus, Haemophilus influenzae, pertussis and pneumococcus antibodies in HIV-infected compared to HIV-uninfected mother-newborn dyads [12, 13, 20, 21, 33]. Although a South African study did not identify an association between transplacental antibody transfer and CD4+ T-lymphocyte counts or HIV-1 viral load ; high maternal HIV-1 viral load was reported to reduce transplacental antibody transfer in another study .
Influenza vaccine and HIV-infected pregnant women
HIV-exposed uninfected infants less than six months have an increased risk of hospitalization and death from respiratory virus-associated lower respiratory tract infections, including influenza virus [2, 9]. In South Africa, two double-blind, randomized, placebo-controlled trials evaluated the safety, immunogenicity and efficacy of a trivalent influenza vaccine in HIV-infected and HIV-uninfected pregnant women, including follow-up of their infants until six months of age . Vaccination of pregnant women with a trivalent influenza vaccine has proven to be safe for both the women and their infants . Before vaccination and one month post-vaccination with the trivalent influenza vaccine, HIV-infected compared to HIV-uninfected pregnant women, had lower hemagglutination-inhibition (HAI) antibody titers and a decreased likelihood of seroconversion (41% vs. 92%, respectively to at least one strain) . Similar observations were reported from a smaller study in the USA, where increased regulatory T-cells numbers were associated with attenuated immune responses to influenza vaccination in HIV-infected women, resulting in reduced immunogenicity to at least one influenza vaccine strain despite similar pre-vaccination HAI titers compared to HIV–uninfected women . Interestingly, high pre-vaccine HAI titers correlated with lower seroconversion rates in HIV-uninfected women, whereas, high pre-vaccine titers correlated with improved seroconversion rates in HIV-infected women . Correlation analyses of post-vaccination HAI titers and HIV viral load in HIV-infected pregnant women, most of whom were on ART, generally have not shown any association [30, 36–38]. Improved immune responses were, however, detected against at least one strain in the trivalent influenza vaccine in women with CD4+ T-lymphocyte counts of >350 cells/μL .
After vaccination with an unadjuvanted 2009 pandemic H1N1 monovalent influenza vaccine, HAI titers were also significantly increased in women with higher CD4+ T-lymphocyte counts [37, 38]. In the study of the 2009 pandemic, H1N1 monovalent influenza vaccination of 130 HIV-infected pregnant women, a second dose of a high-concentration (30 μg/dose) vaccine marginally improved the percentage of women with HAI titers above the putative seroprotective threshold of ≥1:40 and who demonstrated seroconversion (73% and 66% after dose 1 and 80% and 72% after dose 2, respectively). Nevertheless, HIV-infected women still had poorer immune responses than described in HIV-uninfected women . Furthermore, non-pregnant HIV-infected adults had in general poorer immune responses to standard dose (15 μg) of unadjuvanted influenza vaccines compared to HIV-uninfected individuals [39–42].
The inferior immune response to unadjuvant inactivated influenza vaccines in HIV-infected adults has led to investigation for alternate strategies to improve the immune responses to vaccination in this population. Influenza vaccines with higher antigen content elicited higher HAI titers and improved seroresponse rates in HIV-infected non-pregnant adults, however, the responses were still inferior compared to HIV-uninfected adults [43, 44]. Furthermore, a second vaccine dose did not consistently increase the immune responses [40, 41, 43, 45]. Although the safety and immunogenicity of adjuvanted pandemic H1N1 vaccines has not been evaluated in HIV-infected pregnant women, immune responses in non-pregnant HIV-infected adults were better with adjuvanted pandemic H1N1 vaccine compared to unadjuvanted vaccines; this included higher percentage of ASO3-adjuvanted vaccine recipients developing HAI titers ≥1:40 compared to unadjuvanted vaccine–recipients . HAI titers ≥1:40 were 70–93% and increased to 94–99% after 2 doses of the ASO3-adjuvanted vaccine, which was similar to the response described in HIV-uninfected individuals (>95%) [41, 46]. Also, a single dose of a MF59-adjuvanted vaccine was associated with 88% of HIV-infected adults developing HAI titers ≥1:40, which had a small increase to 91% following the second vaccination, which was similar to HIV-uninfected controls . Overall, the HAI GMT titers were, however, lower in HIV-infected than HIV-uninfected adults .
In healthy adults, a HAI titer of 1:40 or higher is associated with 50% protection against influenza disease . However, data from studies on HIV-infected pregnant and non-pregnant adults suggest that influenza vaccination may confer protection to this population by additional mechanisms and that the use of HAI titers as a correlate of protection needs to be validated in these individuals [30, 50]. Furthermore it has been proposed that higher HAI titers may be required to provide protection against influenza in children .
In the South African randomized-controlled trials of trivalent influenza vaccine in pregnant women, the vaccine efficacy against PCR-confirmed influenza was similar in HIV-infected (58%; 95% CI: 0.2, 82) and HIV-uninfected (50%; 95% CI: 15, 71) women despite HIV-infected women having a reduced immune response to vaccination [30, 35]. Two other randomized-controlled trials evaluated the efficacy of trivalent influenza vaccine in pregnant women against influenza infection in the women and their infants until six months of age; however, the only study that measured vaccine efficacy in HIV-infected women was conducted in South Africa [35, 52, 53]. Incidentally, the trial conducted in Bangladesh reported fewer episodes of influenza infection during the first six months of life in infants born to influenza vaccinated pregnant women compared to infants born to women who received 23-valent pneumococcal vaccine; for laboratory confirmed influenza infection in infants the vaccine efficacy was 63% (95% CI: 5, 85) . The two other larger African trials corroborated the protection afforded by maternal vaccination against PCR–confirmed influenza in infants younger than six months. In Mali infants born to women who received influenza vaccine had a lower influenza attack-rate compared to those born to women vaccinated with quadrivalent meningococcal vaccine, with an overall vaccine efficacy of 33% (95% CI: 4, 54) . In South Africa the vaccine efficacy against PCR–confirmed influenza was 49% (95% CI: 12, 70) among infants born to HIV-uninfected women and while the study was not powered to detect vaccine efficacy in the HIV-exposed infants a modest vaccine efficacy point estimate was reported (26.7%; CI: −132, 77) . Based on the immunogenicity data from the two South African trials, despite vaccine efficacy in the HIV-infected mothers (which was similar compared to HIV-uninfected women), alternate strategies to protect the HIV-exposed infants need to be considered. Whilst vaccine induced cell mediated immunity might play a role in adults, protection in the infants will only be mediated by the presence of antibodies; hence higher antibody concentrations need to be elicited in the women.
Group B Streptococcus and maternal HIV-infection
Although recto-vaginal GBS colonization is similar or lower in HIV-infected compared to HIV-uninfected pregnant women [54–56], HEU have a 2–20 fold increase susceptibility of invasive GBS disease compared to HIV-unexposed infants; and particularly so for late-onset disease (disease occurring from 7 to 89 days of life, LOD; 4–125 fold) [7, 57, 58]. Furthermore, HEU compared to HIV-unexposed infants with invasive GBS disease are more likely to present with meningitis than sepsis .
Natural serotype-specific and surface-protein IgG antibodies have been compared between HIV-infected and HIV-uninfected mother-newborn dyads [28, 29]. In two studies conducted in two different regions of South Africa with a high HIV prevalence, serotypes Ia, Ib, II, III and V-specific IgG antibody levels were consistently lower in HIV-exposed compared to HIV–unexposed newborns [28, 29]. This was likely due to the combination of lower maternal antibody concentrations and reduced transplacental antibody transfer between HIV-infected compared to HIV-uninfected mother-newborn pairs. Both studies, although not specifically powered to address the question, reported no associations between the maternal level of immune suppression and anti-GBS epitope antibody levels or transplacental ratios, although most women had CD4+ T-lymphocyte counts >350 cells/mL and were on ART during pregnancy [28, 29]. Furthermore, another recent study from South Africa showed that the proportion of individual IgG subclasses transferred through the placenta was unaffected by maternal HIV infection, with the exception of serotypes III IgG1; and importantly there was no difference in transplacental transfer of IgG2, the main subclass against GBS polysaccharides .
Maternal GBS vaccination is potentially cost effective, both in high income [60, 61] and low-middle income countries . Early experimental conjugate vaccines induced good IgG responses in pregnant women which persisted for long periods and could also protect against LOD [63, 64]. Although there is no licensed GBS vaccine, an investigational trivalent GBS polysaccharide-protein conjugate vaccine that includes serotypes Ia, Ib and III was recently evaluated in a phase-II study among HIV-uninfected and HIV-infected pregnant women [65, 66]. In Malawi (18% maternal HIV prevalence) and South African (30% maternal HIV prevalence), lower vaccine immunogenicity was observed among the HIV-infected compared to HIV-uninfected pregnant women . Among HIV-infected women, immune responses did not differ between those with low (50–350 cells/mL) and high (>350 cells/mL) CD4+ T-lymphocyte counts. Furthermore, antibody concentrations post-vaccination were lower in women without detectable antibody levels at baseline, suggesting an absence of memory lymphocytes in these women. Transplacental antibody transfer and antibody decay was similar between HIV-infected and HIV-uninfected mother-newborn dyads, nevertheless, HIV-exposed infants had lower antibody concentrations than HIV-unexposed infants at birth and at 6 weeks of age . Because a correlate of protection has not been established, it is unknown whether antibody concentrations in HIV-exposed infants are sufficient to protect against invasive GBS disease.
Antibody transfer from mother to fetus is crucial in protecting young infants against various infectious diseases prior to their primary immunization or during the period that they are unable to mount a robust immune response to infection. Poor immune responses to natural infection result in lower antibody levels in HIV-infected women and may contribute to disease susceptibility in HIV-exposed infants. Although maternal vaccination reduces early infant disease, lower immune responses to vaccines have been reported in HIV-infected compared to HIV-uninfected pregnant women; this needs to be considered in vaccine development, especially in settings with high maternal HIV-infection prevalence and regardless of PMTCT or ART. Females who were born with HIV and those on long-term ART would soon be entering child-bearing age; these women need to be further studied as to whether T- and B-cell memory is preserved.
Immunogenicity may be enhanced in HIV-infected women through two-dosing vaccine schedules . The first dose would “re-prime” the HIV-infected women’s immune system and then the second dose would serve as a booster. Higher antigen concentrations and the use of conjugate vaccines have also shown improved immunogenicity and efficacy in HIV-infected adults and may be explored in HIV-infected pregnant women [38, 67]. The use of adjuvants to boost immune responses needs further investigation. Maternal vaccine immunogenicity studies or phase IV efficacy trials, coupled with cost-effectiveness studies must be conducted in HIV-infected pregnant women in highly endemic settings.
Group B Streptococcus
Prevention of mother to child transmission
SAM is funded in part by National Research Foundation/Department of Science and Technology: South African Research Chair Initiative in Vaccine Preventable Diseases and Medical Research Council of South Africa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Availability of data and materials
ZD, MCN, GK, SGL and SAM made substantial contributions to conception and interpretation of data; ZD and MCN drafted the manuscript while GK, SGL and SAM critically revised the manuscript; all authors have given final approval of the version to be published and agreed to be accountable for all aspects of the work.
All authors have no conflicts of interest relevant to this article to disclose.
Consent for publication
Ethics approval and consent to participate
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Luzuriaga K, Mofenson LM. Challenges in the Elimination of Pediatric HIV-1 Infection. N Engl J Med. 2016;374:761–70.View ArticlePubMedGoogle Scholar
- Slogrove AL, Goetghebuer T, Cotton MF, Singer J, Bettinger JA. Pattern of infectious morbidity in HIV-exposed uninfected infants and children. Front Immunol. 2016;7:164.PubMedPubMed CentralGoogle Scholar
- Filteau S. The HIV-exposed, uninfected African child. Trop Med Int Health. 2009;14:276–87.View ArticlePubMedGoogle Scholar
- Evans C, Jones CE, Prendergast AJ. HIV-exposed, uninfected infants: new global challenges in the era of paediatric HIV elimination. Lancet Infect Dis. 2016;16:e92–e107.View ArticlePubMedGoogle Scholar
- Marinda E, Humphrey JH, Iliff PJ, Mutasa K, Nathoo KJ, Piwoz EG, Moulton LH, Salama P, Ward BJ. Child mortality according to maternal and infant HIV status in Zimbabwe. Pediatr Infect Dis J. 2007;26:519–26.View ArticlePubMedGoogle Scholar
- von Mollendorf C, von Gottberg A, Tempia S, Meiring S, de Gouveia L, Quan V, Lengana S, Avenant T, du Plessis N, Eley B, et al. Increased risk for and mortality from invasive pneumococcal disease in HIV-exposed but uninfected infants aged <1 year in South Africa, 2009–2013. Clin Infect Dis. 2015;60:1346–56.Google Scholar
- Cutland CL, Schrag SJ, Thigpen MC, Velaphi SC, Wadula J, Adrian PV, Kuwanda L, Groome MJ, Buchmann E, Madhi SA. Increased Risk for Group B Streptococcus Sepsis in Young Infants Exposed to HIV, Soweto, South Africa, 2004-2008(1). Emerg Infect Dis. 2015;21:638–45.View ArticlePubMedPubMed CentralGoogle Scholar
- Taron-Brocard C, Le Chenadec J, Faye A, Dollfus C, Goetghebuer T, Gajdos V, Labaune JM, Perilhou A, Mandelbrot L, Blanche S, Warszawski J. Increased risk of serious bacterial infections Due to maternal immunosuppression in HIV-exposed uninfected infants in a European country. Clin Infect Dis. 2014;59:1332–45.View ArticlePubMedGoogle Scholar
- Cohen C, Moyes J, Tempia S, Groome M, Walaza S, Pretorius M, Naby F, Mekgoe O, Kahn K, von Gottberg A, et al. Epidemiology of acute lower respiratory tract infection in HIV-exposed uninfected infants. Pediatrics. 2016;137.
- Afran L, Garcia Knight M, Nduati E, Urban BC, Heyderman RS, Rowland-Jones SL. HIV-exposed uninfected children: a growing population with a vulnerable immune system? Clin Exp Immunol. 2014;176:11–22.View ArticlePubMedPubMed CentralGoogle Scholar
- Kruczek A, Cutland CL, Madhi SA. Effect of maternal HIV infection on measles susceptibility during early infancy: implications for optimizing protection of the infant. Future Med. 2010;4:1–12.Google Scholar
- Jones CE, Naidoo S, De Beer C, Esser M, Kampmann B, Hesseling AC. Maternal HIV infection and antibody responses against vaccine-preventable diseases in uninfected infants. JAMA. 2011;305:576–84.View ArticlePubMedGoogle Scholar
- Gupta A, Mathad JS, Yang WT, Singh HK, Gupte N, Mave V, Bharadwaj R, Zaman K, Roy E, Bollinger RC, et al. Maternal pneumococcal capsular IgG antibodies and transplacental transfer are low in South Asian HIV-infected mother-infant pairs. Vaccine. 2014;32:1466–72.View ArticlePubMedPubMed CentralGoogle Scholar
- Chu HY, Englund JA. Maternal immunization. Clin Infect Dis. 2014;59:560–8.View ArticlePubMedPubMed CentralGoogle Scholar
- Demicheli V, Barale A, Rivetti A. Vaccines for women for preventing neonatal tetanus. Cochrane Database Syst Rev. 2015;7:CD002959.Google Scholar
- Steinhoff MC. Assessments of vaccines for prenatal immunization. Vaccine. 2013;31 Suppl 4:D27–30.View ArticlePubMedGoogle Scholar
- McQuaid F, Jones C, Stevens Z, Plumb J, Hughes R, Bedford H, Heath PT, Matthew DS. Attitudes towards vaccination against group B streptococcus in pregnancy. Arch Dis Child. 2014;99:700–1.View ArticlePubMedGoogle Scholar
- Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646.View ArticlePubMedGoogle Scholar
- Leach JL, Sedmak DD, Osborne JM, Rahill B, Lairmore MD, Anderson CL. Isolation from human placenta of the IgG transporter, FcRn, and localization to the syncytiotrophoblast: implications for maternal-fetal antibody transport. J Immunol. 1996;157:3317–22.PubMedGoogle Scholar
- de Moraes-Pinto MI, Almeida AC, Kenj G, Filgueiras TE, Tobias W, Santos AM, Carneiro-Sampaio MM, Farhat CK, Milligan PJ, Johnson PM, Hart CA. Placental transfer and maternally acquired neonatal IgG immunity in human immunodeficiency virus infection. J Infect Dis. 1996;173:1077–84.View ArticlePubMedGoogle Scholar
- Cumberland P, Shulman CE, Maple PA, Bulmer JN, Dorman EK, Kawuondo K, Marsh K, Cutts FT. Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya. J Infect Dis. 2007;196:550–7.View ArticlePubMedGoogle Scholar
- Malek A, Sager R, Kuhn P, Nicolaides KH, Schneider H. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol. 1996;36:248–55.View ArticlePubMedGoogle Scholar
- Boyer KM, Papierniak CK, Gadzala CA, Parvin JD, Gotoff SP. Transplacental passage of IgG antibody to group B streptococcus serotype Ia. J Pediatr. 1984;104:618–20.View ArticlePubMedGoogle Scholar
- Christensen KK, Christensen P, Duc G, Hoger P, Kind C, Matsunaga T, Muller B, Seger RA. Correlation between serum antibody-levels against group B streptococci and gestational age in newborns. Eur J Pediatr. 1984;142:86–8.View ArticlePubMedGoogle Scholar
- Eberhardt CS, Blanchard-Rohner G, Lemaitre B, Boukrid M, Combescure C, Othenin-Girard V, Chilin A, Petre J, de Tejada BM, Siegrist CA. Maternal immunization earlier in pregnancy maximizes antibody transfer and expected infant seropositivity against pertussis. Clin Infect Dis. 2016;62:829–36.View ArticlePubMedPubMed CentralGoogle Scholar
- Black FL, Berman LL, Borgono JM, Capper RA, Carvalho AA, Collins C, Glover O, Hijazi Z, Jacobson DL, Lee YL, et al. Geographic variation in infant loss of maternal measles antibody and in prevalence of rubella antibody. Am J Epidemiol. 1986;124:442–52.PubMedGoogle Scholar
- Dauby N, Goetghebuer T, Kollmann TR, Levy J, Marchant A. Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections. Lancet Infect Dis. 2012;12:330–40.View ArticlePubMedGoogle Scholar
- Le Doare K, Allen L, Kampmann B, Heath PT, Taylor S, Hesseling AC, Gorringe A, Jones CE. Anti-group B Streptococcus antibody in infants born to mothers with human immunodeficiency virus (HIV) infection. Vaccine. 2015;33:621–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Dangor Z, Kwatra G, Izu A, Adrian P, van Niekerk N, Cutland CL, Adam Y, Velaphi S, Lala SG, Madhi SA. HIV-1 Is Associated With Lower Group B Streptococcus Capsular and Surface-Protein IgG Antibody Levels and Reduced Transplacental Antibody Transfer in Pregnant Women. J Infect Dis. 2015;212:453–62.View ArticlePubMedGoogle Scholar
- Nunes MC, Cutland CL, Dighero B, Bate J, Jones S, Hugo A, van Niekerk N, Kuwanda L, Izu A, Weinberg A, Madhi SA. Kinetics of hemagglutination-inhibiting antibodies following maternal influenza vaccination among mothers with and those without HIV infection and their infants. J Infect Dis. 2015;212:1976–87.View ArticlePubMedPubMed CentralGoogle Scholar
- Burton CT, Goodall RL, Samri A, Autran B, Kelleher AD, Poli G, Pantaleo G, Gotch FM, Imami N. Restoration of anti-tetanus toxoid responses in patients initiating highly active antiretroviral therapy with or without a boost immunization: an INITIO substudy. Clin Exp Immunol. 2008;152:252–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Wheatley AK, Kristensen AB, Lay WN, Kent SJ. HIV-dependent depletion of influenza-specific memory B cells impacts B cell responsiveness to seasonal influenza immunisation. Sci Rep. 2016;6:26478.View ArticlePubMedPubMed CentralGoogle Scholar
- Scott S, Cumberland P, Shulman CE, Cousens S, Cohen BJ, Brown DW, Bulmer JN, Dorman EK, Kawuondo K, Marsh K, Cutts F. Neonatal measles immunity in rural Kenya: the influence of HIV and placental malaria infections on placental transfer of antibodies and levels of antibody in maternal and cord serum samples. J Infect Dis. 2005;191:1854–60.View ArticlePubMedGoogle Scholar
- Farquhar C, Nduati R, Haigwood N, Sutton W, Mbori-Ngacha D, Richardson B, John-Stewart G. High maternal HIV-1 viral load during pregnancy is associated with reduced placental transfer of measles IgG antibody. J Acquir Immune Defic Syndr. 2005;40:494–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Madhi SA, Cutland CL, Kuwanda L, Weinberg A, Hugo A, Jones S, Adrian PV, van Niekerk N, Treurnicht F, Ortiz JR, et al. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med. 2014;371:918–31.View ArticlePubMedGoogle Scholar
- Richardson K, Weinberg A. Reduced immunogenicity of influenza vaccines in HIV-infected compared with uninfected pregnant women is associated with regulatory T cells. Aids. 2011;25:595–602.View ArticlePubMedGoogle Scholar
- Weinberg A, Muresan P, Richardson KM, Fenton T, Dominguez T, Bloom A, Watts DH, Abzug MJ, Nachman SA, Levin MJ. Determinants of vaccine immunogenicity in HIV-infected pregnant women: analysis of B and T cell responses to pandemic H1N1 monovalent vaccine. PLoS One. 2015;10:e0122431.View ArticlePubMedPubMed CentralGoogle Scholar
- Abzug MJ, Nachman SA, Muresan P, Handelsman E, Watts DH, Fenton T, Heckman B, Petzold E, Weinberg A, Levin MJ. Safety and immunogenicity of 2009 pH1N1 vaccination in HIV-infected pregnant women. Clin Infect Dis. 2013;56:1488–97.View ArticlePubMedPubMed CentralGoogle Scholar
- Crum-Cianflone NF, Eberly LE, Duplessis C, Maguire J, Ganesan A, Faix D, Defang G, Bai Y, Iverson E, Lalani T, et al. Immunogenicity of a monovalent 2009 influenza A (H1N1) vaccine in an immunocompromised population: a prospective study comparing HIV-infected adults with HIV-uninfected adults. Clin Infect Dis. 2011;52:138–46.View ArticlePubMedPubMed CentralGoogle Scholar
- Lagler H, Grabmeier-Pfistershammer K, Touzeau-Romer V, Tobudic S, Ramharter M, Wenisch J, Gualdoni GA, Redlberger-Fritz M, Popow-Kraupp T, Rieger A, Burgmann H. Immunogenicity and tolerability after two doses of non-adjuvanted, whole-virion pandemic influenza A (H1N1) vaccine in HIV-infected individuals. PLoS One. 2012;7:e36773.View ArticlePubMedPubMed CentralGoogle Scholar
- Launay O, Desaint C, Durier C, Loulergue P, Duval X, Jacomet C, Pialoux G, Ghosn J, Raffi F, Rey D, et al. Safety and immunogenicity of a monovalent 2009 influenza A/H1N1v vaccine adjuvanted with AS03A or unadjuvanted in HIV-infected adults: a randomized, controlled trial. J Infect Dis. 2011;204:124–34.View ArticlePubMedPubMed CentralGoogle Scholar
- Tebas P, Frank I, Lewis M, Quinn J, Zifchak L, Thomas A, Kenney T, Kappes R, Wagner W, Maffei K, Sullivan K. Poor immunogenicity of the H1N1 2009 vaccine in well controlled HIV-infected individuals. Aids. 2010;24:2187–92.View ArticlePubMedGoogle Scholar
- El Sahly HM, Davis C, Kotloff K, Meier J, Winokur PL, Wald A, Johnston C, George SL, Brady RC, Lehmann C, et al. Higher antigen content improves the immune response to 2009 H1N1 influenza vaccine in HIV-infected adults: a randomized clinical trial. J Infect Dis. 2012;205:703–12.View ArticlePubMedPubMed CentralGoogle Scholar
- McKittrick N, Frank I, Jacobson JM, White CJ, Kim D, Kappes R, DiGiorgio C, Kenney T, Boyer J, Tebas P. Improved immunogenicity with high-dose seasonal influenza vaccine in HIV-infected persons: a single-center, parallel, randomized trial. Ann Intern Med. 2013;158:19–26.View ArticlePubMedGoogle Scholar
- Cooper C, Thorne A, Klein M, Conway B, Boivin G, Haase D, Shafran S, Zubyk W, Singer J, Halperin S, Walmsley S. Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults. PLoS One. 2011;6:e17758.View ArticlePubMedPubMed CentralGoogle Scholar
- Cooper C, Klein M, Walmsley S, Haase D, MacKinnon-Cameron D, Marty K, Li Y, Smith B, Halperin S, Law B, et al. High-level immunogenicity is achieved vaccine with adjuvanted pandemic H1N1(2009) and improved with booster dosing in a randomized trial of HIV-infected adults. HIV Clin Trials. 2012;13:23–32.View ArticlePubMedGoogle Scholar
- Soonawala D, Rimmelzwaan GF, Gelinck LB, Visser LG, Kroon FP. Response to 2009 pandemic influenza A (H1N1) vaccine in HIV-infected patients and the influence of prior seasonal influenza vaccination. PLoS One. 2011;6:e16496.View ArticlePubMedPubMed CentralGoogle Scholar
- Nunes MC, Cutland CL, Jones S, Hugo A, Madimabe R, Simoes EA, Weinberg A, Madhi SA. Duration of infant protection against influenza illness conferred by maternal immunization: secondary analysis of a randomized clinical trial. JAMA Pediatr. 2016;170:840–7.View ArticlePubMedGoogle Scholar
- Hobson D, Curry RL, Beare AS, Ward-Gardner A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg (Lond). 1972;70:767–77.View ArticleGoogle Scholar
- Madhi SA, Maskew M, Koen A, Kuwanda L, Besselaar TG, Naidoo D, Cohen C, Valette M, Cutland CL, Sanne I. Trivalent inactivated influenza vaccine in African adults infected with human immunodeficient virus: double blind, randomized clinical trial of efficacy, immunogenicity, and safety. Clin Infect Dis. 2011;52:128–37.View ArticlePubMedGoogle Scholar
- Black S, Nicolay U, Vesikari T, Knuf M, Del Giudice G, Della Cioppa G, Tsai T, Clemens R, Rappuoli R. Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr Infect Dis J. 2011;30:1081–5.View ArticlePubMedGoogle Scholar
- Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, Wilson E, Omer SB, Shahid NS, Breiman RF, Steinhoff MC. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med. 2008;359:1555–64.View ArticlePubMedGoogle Scholar
- Tapia MD, Sow SO, Tamboura B, Teguete I, Pasetti MF, Kodio M, Onwuchekwa U, Tennant SM, Blackwelder WC, Coulibaly F, et al. Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial. Lancet Infect Dis. 2016;16:1026–35.
- Gray KJ, Kafulafula G, Matemba M, Kamdolozi M, Membe G, French N. Group B Streptococcus and HIV infection in pregnant women, Malawi, 2008–2010. Emerg Infect Dis. 2011;17:1932–5.View ArticlePubMedPubMed CentralGoogle Scholar
- Shah M, Aziz N, Leva N, Cohan D. Group B Streptococcus colonization by HIV status in pregnant women: prevalence and risk factors. J Womens Health. 2011;20:1737–41.View ArticleGoogle Scholar
- Cutland CL, Schrag SJ, Zell ER, Kuwanda L, Buchmann E, Velaphi SC, Groome MJ, Adrian PV, Madhi SA. Maternal HIV infection and vertical transmission of pathogenic bacteria. Pediatrics. 2012;6:6.Google Scholar
- Epalza C, Goetghebuer T, Hainaut M, Prayez F, Barlow P, Dediste A, Marchant A, Levy J. High incidence of invasive group B streptococcal infections in HIV-exposed uninfected infants. Pediatrics. 2010;126:23.View ArticleGoogle Scholar
- Dangor Z, Lala SG, Cutland CL, Koen A, Jose L, Nakwa F, Ramdin T, Fredericks J, Wadula J, Madhi SA. Burden of invasive group B streptococcus disease and early neurological sequelae in South african infants. PLoS One. 2015;10:e0123014.View ArticlePubMedPubMed CentralGoogle Scholar
- Le Doare K, Taylor S, Allen L, Gorringe A, Heath PT, Kampmann B, Hesseling AC, Jones CE. Placental transfer of anti-group B Streptococcus immunoglobulin G antibody subclasses from HIV-infected and uninfected women to their uninfected infants. Aids. 2016;30:471–5.View ArticlePubMedPubMed CentralGoogle Scholar
- Mohle-Boetani JC, Schuchat A, Plikaytis BD, Smith JD, Broome CV. Comparison of prevention strategies for neonatal group B streptococcal infection. A population-based economic analysis. JAMA. 1993;270:1442–8.View ArticlePubMedGoogle Scholar
- Oster G, Edelsberg J, Hennegan K, Lewin C, Narasimhan V, Slobod K, Edwards MS, Baker CJ. Prevention of group B streptococcal disease in the first 3 months of life: would routine maternal immunization during pregnancy be cost-effective? Vaccine. 2014;32:4778–85.View ArticlePubMedGoogle Scholar
- Kim SY, Russell LB, Park J, Verani JR, Madhi SA, Cutland CL, Schrag SJ, Sinha A. Cost-effectiveness of a potential group B streptococcal vaccine program for pregnant women in South Africa. Vaccine. 2014;32:1954–63.View ArticlePubMedGoogle Scholar
- Baker CJ, Rench MA, McInnes P. Immunization of pregnant women with group B streptococcal type III capsular polysaccharide-tetanus toxoid conjugate vaccine. Vaccine. 2003;21:3468–72.View ArticlePubMedGoogle Scholar
- Edwards MS, Lane HJ, Hillier SL, Rench MA, Baker CJ. Persistence of functional antibodies to group B streptococcal capsular polysaccharides following immunization with glycoconjugate vaccines. Vaccine. 2012;30:4123–6.View ArticlePubMedPubMed CentralGoogle Scholar
- Madhi SA, Cutland CL, Jose L, Koen A, Govender N, Wittke F, Olugbosi M, Meulen AS, Baker S, Dull PM, et al. Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in healthy women and their infants: a randomised phase 1b/2 trial. Lancet Infect Dis. 2016;16:923–34.
- Heyderman RS, Madhi SA, French N, Cutland C, Ngwira B, Kayambo D, Mboizi R, Koen A, Jose L, Olugbosi M, et al. Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial. Lancet Infect Dis. 2016;16:546–55.View ArticlePubMedPubMed CentralGoogle Scholar
- French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, Mwaiponya M, Zijlstra EE, Molyneux ME, Gilks CF. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med. 2010;362:812–22.View ArticlePubMedPubMed CentralGoogle Scholar