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1 Maternal Immunization: Protecting Mother and Baby Thursday, August 10, :00 PM ET In Case of Technical Difficulties If you hear an echo: Make sure you are only logged in once on your computer Select one form of audio only (either computer speakers or telephone connection) If the audio is choppy: Press pause in the top left corner of your screen Wait 10 seconds and then click the play button Dial at any time for live assistance 1

2 Agenda Agenda Welcome and Introductions William Schaffner, MD NFID Medical Director Professor of Preventive Medicine and Infectious Diseases Vanderbilt University School of Medicine Nashville, TN Maternal Immunization: Protecting Mother and Baby C. Mary Healy, MD Associate Professor of Pediatrics Infectious Disease Section Baylor College of Medicine Houston, TX Questions and Answers This webinar is supported by an unrestricted educational grant from Merck & Co., Inc. NFID policies restrict funders from controlling program content. General Information Please note that today s webinar is being recorded All phone lines will be placed on mute throughout the program To hear audio: Computer: Follow directions Phone: ; Access Code After the presentations, there will be a Question and Answer period Use the Chat box on the lower left side of your screen to type your question At the end of the webinar, participants will be directed to an online evaluation Following the webinar, all registered participants will receive an with a link to the presentation slides 2

3 CE Credit & Webinar Evaluation The National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. NFID designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit TM This continuing nursing education activity was approved by the Ohio Nurses Association, an accredited approver by the American Nurses Credentialing Center s Commission on Accreditation (OBN ). This education activity has been approved for a maximum of 1.o contact hour. To receive credit or contact hours, you must complete the online evaluation and pass the post-test with a score of 80% or higher Online evaluation and post-test will be available following the webinar at: Certificate will be available for print or download following successful completion of online evaluation and post-test until August 10, 2018 Disclosures Marla Dalton (NFID staff, content reviewer) owns stock, stock options, or bonds from Merck & Co., Inc. William Schaffner (NFID medical director, presenter) served as an advisor or consultant for Dynavax, GSK, Merck & Co., Inc., Novavax, Inc., Pfizer Inc., Sanofi Pasteur, and Seqirus All other activity planners/reviewers and staff for this activity have no relevant financial relationships to disclose 3

4 Learning Objectives At the conclusion of this activity, participants will be able to: Describe the rationale for maternal immunization Outline current maternal immunization recommendations for influenza and pertussis and discuss their impact on maternal and infant infection Discuss strategies to improve uptake of vaccines in pregnant women About NFID Non-profit 501(c)(3) organization dedicated to educating the public and healthcare professionals about causes, treatment, and prevention of infectious diseases across the lifespan Reaches consumers, healthcare professionals, and media through: Coalition-building activities Public outreach initiatives Professional educational programs (ACCME accredited with commendation) Scientific meetings, research, and training Longstanding partnerships to facilitate rapid program initiation and increase programming impact Flexible and nimble organization 4

5 Maternal Immunization: Protecting Mother and Baby Wednesday, October 5, :00 PM ET C. Mary Healy, MD Associate Professor of Pediatrics Infectious Disease Section Baylor College of Medicine Houston, TX Reality Pregnant women and their young infants are at risk from vaccine-preventable diseases (VPD) 1,2 Many VPDs are more severe in neonates and young infants than in other age groups 1,2 Neonatal immunization is a limited strategy 1 Variable immune responses due to immaturity Multiple doses of vaccine are still needed Disease can precede immunological response Maternal immunization offers the prospect of a 2 for 1 strategy 1,2 1 Clin Obstet Gynecol. 2012;55: Clin Infect Dis. 2014;59:

6 Maternal Immunization Is Not A New Concept 1879: Vaccinia Virus 1938: Whole cell pertussis vaccine 1,2 1961: Tetanus vaccine 1,2 millions of mother and infant lives saved 1964: First US maternal immunization with influenza vaccine recommendation for protection of the woman 3 1 Clin Obstet Gynecol. 2012;55: Clin Infect Dis. 2014;59: Public Health Rep. 1964; 75:944. But It Is Complicated In resource-rich countries 1,2 Potential risk perceived to overshadow benefit Licensing pathways are lacking Manufacturers are concerned about liability, despite the fact that the National Vaccine Compensation Program covers vaccine-associated injuries in mother/fetus Historically, obstetrical care providers not vaccinators In resource-poor countries 1,2 Lack of trust in government Cultural barriers Although many medical contacts during pregnancy, not an established immunization platform 1 1 Clin Obstet Gynecol. 2012;55: Clin Infect Dis. 2014;59:

7 Barriers to Maternal Immunization Medication tragedies harming the fetus FDA doesn t have licensing pathways Manufacturers remain concerned about liability Lack of awareness about VPDs Healthcare professionals and patients Perceived unwillingness among pregnant women Concerns about extra time to educate and vaccinate, reimbursement, storing vaccines Biological Considerations Placental transport is a selective process using receptor-mediated transport 1,2 IgG 1 = IgG 3 > IgG 2 > IgG 4 Protein antigens elicit IgG 1 and IgG 3 ; PS antigens elicit IgG 2 Begins at 17 weeks and increases throughout gestation (passive transport) 1,2 By 33 weeks maternal levels equal fetal levels By 40 weeks total fetal IgG exceeds maternal levels (active transport) Placental abnormalities affect transport 1,2 HIV, malaria, coexisting infections 1 Clin Obstet Gynecol. 2012;55: Clin Infect Dis. 2014;59:

8 Mimicking Nature s Gift Reproduced with permission: N. Engl. J. Med: 2001; 345: : Considerations for Implementation Safety for mother and infant 1,2 Immunogenicity 1,2 Placental transfer 2 Timing may be important 2 Disease burden 2 Maternal > Infant Infant > Maternal Clin Obstet Gynecol. 2012;55:

9 Vaccines Recommended for All Pregnant Women Inactivated Influenza Vaccine (IIV) Pertussis (Tdap in the US) Tetanus Vaccines Recommended For Pregnant Women In Special Circumstances 1 When risk of infection is high Underlying predisposing condition Travel to endemic area Outbreak Occupational or lifestyle exposure Examples include: Hepatitis A and B; Meningococcal PS; Pneumococcal PS; Rabies Cautiously recommended when risks are high IPV; anthrax; JE; Yellow fever 1 9

10 Vaccines Recommended for All Pregnant Women Inactivated Influenza Vaccine (IIV) Pertussis (Tdap in the US) Tetanus Influenza Recommendations 1 IIV should be administered to any woman who is or might be pregnant during the influenza season IIV may be administered at any time during pregnancy Live influenza influenza vaccine (LAIV) should not be administered during pregnancy 1 MMWR 2016; 65:

11 Maternal-Young Infant Influenza Burden of disease substantial fold increased risk of complications and death in pregnant women (typically in 2 nd and 3 rd trimester) If little maternal influenza-specific IgG, increased risk of complicated influenza in young infant 1-3 No infant vaccine until 6 months doses, 4 weeks apart (uptake is suboptimal) IIV recommended for all pregnant women uptake ~15% H1N1 pandemic ~50% 1 Clin Obstet Gynecol. 2012;55: Clin Infect Dis. 2014;59: MMWR 2016; 65:1 54 Influenza and Pregnant Women Increased susceptibility to complications 1,2 Altered respiratory capacity Depressed cellular immunity Increased risk of hospitalization compared to non-pregnant women 1,2 During the 2009 pandemic, 20% of hospitalized pregnant women died 3 Increased risk of spontaneous abortion, preterm delivery, low birth weight infant MMWR 2016; 65: Clin Infect Dis. 2014;59: MMWR 2011;60:

12 Safety of Influenza Vaccine Fell et al. 1 reported 22,340 pregnant women who were given influenza vaccine; found that compared to the infants of unvaccinated women infants of vaccinated were less likely to be Small for gestational age (RR 0.9) < 32 weeks gestation (RR 0.73) Experience fetal death (RR 0.66) No increased risk for fetal anomalies when influenza vaccine given in pregnancy, including first trimester 2,3 Systematic reviews confirm these findings 4 1 Am J Public Health 2012;102:e33 2 JAMA 2012:308: J Pediatr. 2017;187: BJOG 2015;122:17-26 Benefits of Maternal IIV Vaccine For Neonates and Infants Are Striking Reduces risk of prematurity by 40% 1 Reduces the risk of being small for gestational age 1 Reduces influenza-related hospitalization by 81-90% 2,3 Reduces influenza-like illness by 64% 3 1 PLOS Med 2011;8:5 2 Clin Infect Dis 2010;51: Pediatrics 2016; 137:e

13 Vaccines Recommended for All Pregnant Women Inactivated Influenza Vaccine (IIV) Pertussis (Tdap in the US) Tetanus Pertussis Recommendations Tdap should be administered during each pregnancy, preferably during weeks 27 through 36 gestation, regardless of a women s history of prior receipt of Tdap (or Td) Tdap should be administered postpartum to women who have never received Tdap or whose vaccination history is unknown Infant contacts (father, family members, caregivers) should be brought up to date with recommended pertussis vaccines, ideally 2 weeks prior to infant contact 13

14 Pertussis A Poorly Controlled Vaccine-Preventable Disease Cyclical incidence with peaks every 3-5 years Immunity (natural and vaccine-induced) wanes Highly contagious Infection may be unrecognized atypical or asymptomatic in adolescents and young adults Improved detection methods Change to acellular pertussis vaccine? Variations in B. pertussis? Worldwide Problem US Australia England & Wales Portugal 14

15 Pertussis Infection Who Is At Risk? Images courtesy of vaccine.texaschildrens.org Pertussis-Related Mortality Who Is At Risk? Images courtesy of vaccine.texaschildrens.org 15

16 Pertussis in Infants Infants too young to have completed the primary immunization series have 20 times higher risk of pertussis 1-3 Complications are highest in infants age < 6 months 1,4 Deaths occur almost exclusively in infants age < 3 months 1,2 1 JAMA 2003; 290:: ; 2 MMWR 2009; 57: Provisional Pertussis Surveillance Report 4 Pediatrics 2008;121: Image courtesy of vaccine.texaschildrens.org Pertussis in Young Infants 1,2 Hospitalized Pneumonia Seizures Encephalopathy Deaths 70% 60% 50% 40% 30% 20% 10% % < 6 mo 6-11 mo 1-4 yrs 5-9 yrs yrs 20 yrs Age MMWR 2002; 51:616-8 Image courtesy of the National Foundation for Infectious Diseases (NFID) 16

17 Maternal Pertussis Immunization Safe for mother and infant 1-5 Single center, managed care organizations, national surveillance system data Safe when repeated doses given 4 and when given with IIV 5 Immunogenic in randomized controlled trials and prospective cohort studies 6-11 Significantly higher antibody levels in infants at birth and through 2 months of age 6-11 Some studies show mild interference with infant response to the DTaP series, this appears to be clinically insignificant 12,13 1 BMJ. 2014;349:g4219; 2 Hum Vaccin Immunother. 2015;11:2872-9; 3 JAMA. 2014;312: JAMA. 2015;314:1581-7; 5 Obstet Gynecol. 2015;126: JAMA. 2014;311: ; 7 Vaccine. 2016;34:151-9; 8 Vaccine. 2014;32: ; 9 Vaccine. 2016;34: Vaccine. 2015;33: Open Forum Infect Dis 2015; 2 (suppl 1): S517 doi: /ofid/ofv Clin Infect Dis. 2015;61: Clin Infect Dis. 2015;61: England & Wales Starting October 2012, recommended that pregnant women receive Tdap in weeks gestation Uptake rates quickly reached approximately 60%

18 Effect on Infant Pertussis England & Wales 1 Infants < 3 months of age Vaccine Effectiveness* Maternal Vaccination at least 7 days before birth 91% (84-95) Infants < 3 months of age by timing of maternal immunization Maternal Vaccination at least 28 days before birth Maternal Vaccination at least 7 days before birth Maternal Vaccination 0-6 days before or 1-13 days after birth Infants < 2 months of age 91% (83-95) 91% (70-96) 38% (-95-80) Maternal Vaccination at least 7 days before birth 90% (82-95) * Vaccine Effectiveness % (95% Confidence Intervals) 1 Lancet 2014; 384: Effect on Infant Pertussis California Prenatal Tdap more effective than postpartum Tdap in preventing infant pertussis 1 Timing of Prenatal Tdap VE * infants < 8 weeks VE * infants < 12 weeks weeks gestation 85.4% ( ) 71.7% ( ) Any time in pregnancy 63.8% ( ) 53% ( ) * Vaccine Effectiveness % (95% Confidence Intervals) More effective when given in 3 rd than in 2 nd trimester Infected infants of vaccinated mothers: 2 Were less likely to be hospitalized Had significantly shorter hospital stays Did not require intubation Did not die from pertussis 1 Clin Infect Dis 2017;64:3-8 2 Clin Infect Dis 2017;64:

19 May Not Prevent Pertussis In Subsequent Infants Tdap-induced antibodies wane relatively quickly 1 Neonates and young infants can only rely on maternal antibodies for protection until active immunization 2 Serological correlates of protection are unknown but are likely higher in newborn infants than in immunized children and adults who can mount a robust immune response 2 1 Clin Infect Dis. 2013;56: Hum Vaccin Immunother. 2016;12: Limitations of Maternal Tdap Current vaccines do not have optimal immunogenicity 1 Timing of immunization important in infant protection Current data suggest immunizing early in the third trimester is superior to later 2-4 Second trimester? 5 Durability of Tdap-induced maternal antibody in infants is not known 1 Lack of a serological correlate of protection 1 Poor uptake? Effect on infant response 6 1 Hum Vaccin Immunother. 2016;12: Vaccine 2014; 32: Vaccine 2015; 33: Open Forum Infect Dis 2015; 2:S517 5 Clin Infect Dis 2016;62: Clin Infect Dis. 2015;61:

20 Maternal Immunization Works! Reality Why Is IIV & Tdap Uptake So Low In Pregnant Women? 1,2 Healthcare professionals perceive women do not want to be vaccinated during pregnancy Failure to hear a strong recommendation from the obstetrical care provider Inadequate education of OB care providers Time and confidence to discuss vaccination, reimbursement, vaccine ordering, storage 1 Clin Obstet Gynecol. 2012;55: Clin Infect Dis. 2014;59:

21 Reasons Pregnant Women Refuse Vaccines: The Influenza Experience 1,2 Safety risks to the baby The flu vaccine will give me the flu I don t think the vaccine is effective Safety risks to me The flu is not a serious illness 1 MMWR. 2011;60: Vaccine 2013; 31: Motivation For A Healthy Pregnancy CDC: Public Health Image Library 21

22 Provider Recommendation Is Key Factors that influence a pregnant woman s ultimate decision regarding immunization (0=not important; 5=very important) Fear of shots Cost 5 Extra time for visit Adequate Information Safe for Me Safe for Baby 0% 20% 40% 60% 80% 100% 83% said they would receive a vaccine if their provider recommended it Adapted from: Vaccine. 2015;33: The Reality About Uptake Pregnant women motivated to improve their health 1 Pregnant women are willing to get vaccines 2-8 Many opportunities for vaccine discussions (for example, 14 visits are recommended by ACOG) Influenza infection risks the health of mother and baby, but influenza vaccine does not Pertussis related deaths occur almost exclusively in infants 3 months of age Maternal immunization is safe and effective 1 Public Health Rep 2013;128:179; 2 Guidelines for Perinatal Care 7 th ed. 2012; 3 Vaccine. 2015;33: ; 4 Hum Vaccin Immunother. 2015:0. [Epub]; 5 Vaccine. 2013;31:3972-8; 6 Qual Health Res. 2015;25: ; 7 Hum Vaccin Immunother. 2013;9: ; 8 Vaccine. 2014;32:

23 Turning Nature s Gift Into Reality 1,2 Advocate Talk with patients directly Recommend vaccines Identify Use paper or E-prompts to identify patients who need vaccines Educate and Vaccinate Educate clinical and office staff Immunize staff Integrate: Standing Orders, Documentation 1 ACOG committee opinion no. 558: Integrating immunizations into practice. 2 Obstet Gynecol. 2013;121(4): Images courtesy of the National Foundation for Infectious Diseases (NFID) New Maternal Vaccines? 1-3 Group B streptococci (GBS) is a leading cause of early and late-onset infant infections since 1973 The first study of a candidate GBS vaccine for pregnant women was published in 1977 Phase I and II GBS glycoconjugate trials were completed in 2002 Phase 3 trials of CRM197-CPS conjugate those underway Other candidate vaccines; pilus proteins, other proteins, protein CPS conjugates 1 J Infect. 2016;72:S Vaccine 2016; 34: Lancet Infect Dis. 2016;16:

24 Possibilities For The Future 1,2 Vaccine Safe Immunogenic (mothers) Meningococcal (polysaccharide) Pneumococcal (polysaccharide) Group B Streptococcus (conjugate) Haemophilus influenzae type b (polysaccharide) Haemophilus influenzae type b (conjugate) Meningococcal conjugate Pneumococcal conjugate Placental Transport Antibodies Persist Stage of study Y Y 30-56% 3-4 months Phase 1 Y Variable by serotype 24-89% Y Phase 1 Y Y 77% >/= 2 months Phase 2-3 Y Y 44% 4-6 months Phase 1 Y Y 35-62% 4-6 months Phase 1 ND ND ND ND ND ND ND ND ND ND RSV Y Moderately >100% 6 months Phase 1 Adapted from: 1 Clin Obstet Gynecol. 2012;55: J Infect. 2016;72:S83-90 Conclusions Maternal Immunization to prevent neonatal infections is a reality There is hope for future prevention strategies through expansion of current maternal platform Real challenges exist : Understanding drivers of maternal-child health policy decisions Operational research into feasibility Need for expertise in diverse areas Funding Vaccines that benefit mother and infant are a winwin, 2 for 1 strategy 24

25 Questions & Answers Register at: Early Registration Closes on 9/25/17 New for Fall 2017: Call for Poster Abstracts (9/6/17 Submission Deadline) CE Credit & Webinar Evaluation The National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. NFID designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit TM This continuing nursing education activity was approved by the Ohio Nurses Association, an accredited approver by the American Nurses Credentialing Center s Commission on Accreditation (OBN ). This education activity has been approved for a maximum of 1.o contact hour. To receive credit or contact hours, you must complete the online evaluation and pass the post-test with a score of 80% or higher Online evaluation and post-test will be available following the webinar at: Certificate will be available for print or download following successful completion of online evaluation and post-test until August 10,

26 Join Us For Upcoming NFID Webinars The Role of Healthcare Professionals in Protecting Older Adults against Influenza (non CE) Wednesday, September 6, 2017 at 12:00 PM ET Hepatitis ABC s Wednesday, October 18, 2017 at 12:00 PM ET Registration: Subscribe to NFID updates: 26