Current evidence regarding efficacy and safety of human papillomavirus 9-valent (9vHPV), recombinant zoster (RZV), and CpG-adjuvanted recombinant hepatitis B (HepB-CpG) vaccines in adults with human immunodeficiency virus, inflammatory bowel disease, solid organ transplant, and allogeneic hematopoietic stem cell transplant is reviewed.
Summary:
Patients immunocompromised due to underlying disease or treatment are at increased risk for infections; however, insufficient understanding of various vaccines’ efficacy, safety, indications, and contraindications in this population has led to suboptimal vaccination rates. The Infectious Disease Society of America (IDSA) published guidelines on vaccines in immunocompromised populations in 2013. Since then, several advances have been made including an expanded indication with 9vHPV for use in males and females 9 to 45 years old, and the introduction of new vaccines for herpes zoster (RZV) and hepatitis B (HepB-CpG). Pharmacists are instrumental to vaccination efforts and may benefit from a review of recent vaccine updates.
Conclusion:
The 9vHPV can be used in men and women ages 9 to 45 years old regardless of immune status. RZV safety and efficacy in several immunocompromised populations has been demonstrated; however, manufacturers and major societies have yet to update their recommendations. HepB-CpG may be used in most immunocompromised patients yet remains under-utilized.
Immunization and infectious disease. Office of Disease Prevention and Health Promotion: Washington DC. Published2019. www.healthypeople.gov
2.
WasanSKCoukosJAFarrayeFA. Vaccinating the inflammatory bowel disease patient: deficiencies in gastroenterologists’ knowledge. Inflamm Bowel Dis. 2011;17(2):2536–2540.
3.
WasanSKCalderwoodAHLongMDKappelmanMDSandlerRSFarrayeFA. Immunization rates and vaccine beliefs among inflammatory bowel disease patients: an opportunity for improvement. Inflamm Bowel Dis. 2014;20(2):246–250.
4.
JohnsonDRNicholKLLipcynskiK. Barriers to adult immunization. Am J Med. 2006;121(7 suppl 2): S28–S35.
5.
GluckT. Vaccinate your immunocompromised patients!Rheumatology. 2006;45(1):9–10.
6.
RubinLGLevinMJLjungmanP, et al.2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):309–318.
7.
BaroyJChungDFrischRApgarDSlackMK. The impact of pharmacist immunization programs on adult immunization rates: a systematic review and meta-analysis. J Am Pharm Assoc. 2016;56(4):418–426.
8.
BlumlBBrockKAHamstraSTonreyL. Evaluation of the impact of an innovative immunization practice model designed to improve population health: results of the project IMPACT immunizations pilot. Popul Health Manag. 2018:21(1):55–62.
Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins for persons with altered immunocompetence. MMWR Recomm Rep. 1993;42(RR-4):1–18.
11.
KimDKHunterP. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older—United States, 2019. MMWR Morb Mortal Wkly Rep. 2019;68(5):115–118.
12.
Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Published2019. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf
13.
FarrayeFAMelmedGYLichtensteinGRKaneSV. ACG clinical guideline: preventive care in inflammatory bowel disease. Am J Gastroenterol. 2007;112(2):241–248.
14.
Danziger-IsakovLKumarD; AST ID Community of Practice. Vaccination of solid organ transplant candidates and recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13563.
15.
TomblynMChillerTEinseleH, et al.Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Bone Marrow Transplant. 2009;44(8):453–455.
16.
LjungmanPCordonnierCEinseleH, et al.Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2009;44(8):521–526.
17.
CordonnierCEinarsdottirSCesaroS, et al.Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019;19(6):e200–e212.
18.
ReusserNMDowningCGuidryJTyringSK. HPV carcinomas in immunocompromised patients. J Clin Med. 2015;4(2):260–281.
19.
JamiesonDJDuerrABurkR, et al.Characterization of genital human papillomavirus infection in women who have or who are at risk of having HIV infection. Am J Obstet Gynecol. 2002;186(1):21–27.
20.
KimSCGlynnRJGiovannucciE, et al.Risk of high-grade cervical dysplasia and cervical cancer in women with systemic inflammatory diseases: a population-based cohort study. Ann Rheum Dis. 2015;74(7):1360–1367.
21.
Centers for Disease Control and Prevention. Cancers associated with human papillomavirus, United States, 2012–2016 United States Cancer Statistics Data Brief. 2019;10. 2019.
22.
SaraiyaMUngerERThompsonTD, et al.HPV Typing of Cancers Workgroup. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. J Natl Cancer Inst. 2015;107(6):djv086.
23.
JouraEAGiulianoARIversenOE, et al.A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711–723.
24.
Chin-HongPVReidGE. Human papillomavirus infection in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant. 2019;33(9):e13590.
GiulianoARPalefskyJMGoldstoneS, et al.Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med. 2011;364(5):401–411.
27.
Center for Biologics Evaluation and Research. December 10, 2014 Approval Letter -GARDASIL 9. December 10, 2014 Approval Letter -GARDASIL 9. U.S. Food & Drug Administration. Published2018
28.
MuñozNManalastasRPitisuttithumP, et al.Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial. Lancet. 2009;373(9679):1949–1957.
29.
GiulianoARIsaacs-SorianoKTorresBN, et al.Immunogenicity and safety of Gardasil among mid-adult aged men (27-45 years)—The MAM Study. Vaccine. 2015;33(42):5640–5646.
30.
LevinMJMoscickiABSongLY, et al.Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old. J Acquir Immune Defic Syndr. 2010;55(2):197–204.
31.
WilkinTLeeJYLensingSY, et al.Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men. J Infect Dis. 2010;202(8):1246–1253.
32.
KahnJAXuJKapogiannisBG, et al.Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. Clin Infect Dis. 2013;57(5):735–744.
33.
JacobsonDLBousvarosAAshworthL, et al.Immunogenicity and tolerability to human papillomavirus-like particle vaccine in girls and young women with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(7):1441–1449.
34.
KumarDUngerERPanickerGMedvedevPWilsonLHumarA. Immunogenicity of quadrivalent human papillomavirus vaccine in organ transplant recipients. Am J Transplant. 2013;13(9):2411–2417.
35.
NelsonDRNeuAMAbrahamAAmaralSBatiskyDFadrowskiJJ. Immunogenicity of human papillomavirus recombinant vaccine in children with CKD. Clin J Am Soc Nephrol. 2016;11(5):776–784.
36.
MokCCHoLYFongLSToCH. Immunogenicity and safety of a quadrivalent human papillomavirus vaccine in patients with systemic lupus erythematosus: a case–control study. Ann Rheum Dis. 2013;72(5):659–664.
37.
StrattonPBattiwallaMTianX, et al.Immune response following quadrivalent human papillomavirus vaccination in women after hematopoietic allogenic stem cell transplant: a nonrandomized clinical trial. JAMA Oncol. 2020;6(5):1–10.
38.
LiuEYSmithLMEllisAK, et al.Quadrivalent human papillomavirus vaccination in girls and the risk of autoimmune disorders: the Ontario grade 8 HPV vaccine cohort study. CMAJ. 2018;190(21): E648–E655.
39.
GarlandSMBrothertonJMLMoscickiAB, et al.HPV vaccination of immunocompromised hosts. Papillomavirus Res. 2017;4:35–38.
40.
MeitesESzilagyiPGChessonHWUngerERRomeroJRMarkowitzLE. Human papillomavirus vaccination for adults: updated recommendations of the advisory committee on immunization Practices. MMWR Recomm Rep. 2019;68(32);698–702.
41.
SinghJAFurstDEBharatA, et al.2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res. 2012; 64(5):625–639.
42.
MacintyreCRShawPMackieFE, et al.Immunogenicity and persistence of immunity of a quadrivalent human papillomavirus (HPV) vaccine in immunocompromised children. Vaccine. 2016;34(36):4343–4350.
43.
Hidalgo-TenorioCRamírez-TaboadaJGil-AnguitaC, et al.Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine in HIV-positive Spanish men who have sex with men (MSM). AIDS Res Ther. 2017;14(1):34.
44.
MarkowitzLEDunneEFSaraiyaM, et al.Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014;63(RR-05):1–30.
McKaySLGuoAPergamSADoolingK. Herpes zoster risk in immunocompromised adults in the United States: a systematic review [published online ahead of print]. Clin Infect Dis. 2019:ciz1090.
47.
DworkinRHJohnsonRWBreuerJ, et al.Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44(suppl 1):S1–S26.
48.
SymoniakMRFarrokhPGandhiMASlishJC. Herpes zoster subunit vaccine for the prevention of herpes zoster. Am J Health Syst Pharm. 2018;75(12):861–869.
CostaEBuxtonJBrownJTempletonKEBreuerJJohannessenI. Fatal disseminated varicella zoster infection following zoster vaccination in an immunocompromised patient. BMJ Case Rep. 2016;2016:bcr2015212688.
51.
AlexanderKETongPLMacartneyKBeresfordRSheppeardVGuptaM. Live zoster vaccination in an immunocompromised patient leading to death secondary to disseminated varicella zoster virus infection. Vaccine. 2018;36(27):3890–3889.
LalHCunninghamALGodeauxO, et al.Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087–2096.
56.
CunninghamALLalHKovacM, et al.Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375(11):1019–1032.
57.
BerkowitzEMMoyleGStellbrinkHJ, et al.Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled study. J Infect Dis. 2015;211(8):1279–1287.
58.
CurranDMatthewsSRowleySD, et al.Recombinant zoster vaccine significantly reduces the impact on quality of life caused by herpes zoster in adult autologous hematopoietic stem cell transplant recipients: a randomized placebo-controlled trial (ZOE-HSCT). Biol Blood Marrow Transplant. 2019;25(12):2474–2481.
59.
StadtmauerEASullivanKMMartyFM, et al.A phase 1/2 study of an adjuvanted varicella zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients. Blood. 2014;124(19):2921–2929.
60.
DagnewAFIlhanOLeeWS, et al.Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. Lancet Infect Dis. 2019;19(9):988–1000.
61.
BastidasAde la SernaJEl IdrissiM, et al.Effect of recombinant zoster vaccine on incidence of herpes zoster after autologous stem cell transplantation: a randomized clinical trial. JAMA. 2019;322(2):123–133.
62.
SatyamVRPei-HsuanLReichJ, et al.Safety of recombinant zoster vaccine in patients with inflammatory bowel disease [published online ahead of print]. Dig Dis Sci. 2020.
63.
BarghashMHTaimurSRanaMBeharJ. Recombinant herpes zoster vaccine (RZV) after heart transplantation: a single center experience. J Heart Lung Transplant. 2020;39(4): S204.
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29—Identifier NCT03798691, Immunogenicity of herpes zoster subunit vaccine in inflammatory bowel disease patients treated with vedolizumab. https://clinicaltrials.gov/ct2/show/NCT03798691?intr=shingrix&draw=1&rank=3.
VinkPDelgado MingoranceIMaximiano AlonsoC, et al.Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: a randomized trial. Cancer. 2019;125(8):1301–1312.
69.
VinkPRamon TorrellJMSanchez FructuosoA, et al.Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in chronically immunosuppressed adults following renal transplant: a phase 3, randomized clinical trial [published online ahead of print]. Clin Infect Dis. 2019.
70.
DoolingKLGuoAPatelM, et al.Recommendations of the advisory committee on immunization practices for use of herpes zoster vaccine. MMWR Morb Mortal Wkly Rep. 2018;67(3):103–108.
Razavi-ShearerDGamkredlidzeINguyenMH, et al.Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3(6):383–403.
73.
DienstagJL. Hepatitis B virus infection. N Engl J Med. 2008;359(14):1486–1500.
74.
CroaghCMLubelJS. Natural history of chronic hepatitis B: phases in a complex relationship. World J Gastroenterol. 2014;20(30):10395–10404.
75.
PolS. Management of HBV in immunocompromised patients. Liver Int. 2013;33(suppl 1):182–187.
76.
Centers for Disease Control and Prevention. Recommendation of the Immunization Practices Advisory Committee (ACIP) inactivated hepatitis B virus vaccine. MMWR. 1982;31(24):317–322, 327–328.
77.
HuprikarSDanziger-IsakovLAhnJ, et al.Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. Am J Transplant. 2015;15(5):1162–1172.
78.
AroraSKippGBhanotNSureshkumarKK. Vaccinations in kidney transplant recipients: clearing the muddy waters. World J Transplant. 2019;9(1):1–13.
LeeJHHongSImJHLeeJ-SBaekJHKwonHY. Systematic review and meta-analysis of immune response of double dose of hepatitis B vaccination in HIV-infected patients. Vaccine. 2020;38(24):3995–4000.
81.
LaunayOvan der VlietDRosenbergAR, et al.Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA. 2011;305(14):1432–1440.
82.
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29—Identifier NCT03511794, Effectiveness of the hepatitis b vaccine post-hematopoietic stem cell transplant. https://clinicaltrials.gov/ct2/show/NCT03511794
83.
HalperinSAMcneilSLangleyJM, et al.Safety and immunogenicity of different two-dose regimens of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in healthy young adults. Vaccine. 2012;30(36):5445–5448.
84.
HalperinSAWardBCooperC, et al.Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age. Vaccine. 2012;30(15):2556–2563.
85.
JacksonSLentinoJKoppJ, et al.Immunogenicity of a two-dose investigational hepatitis B vaccine, HbsAg-1018, using a toll receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018;36(5):668–674.
86.
SchillieSHarrisALink-GellesRRomeroJWardJNelsonN. Recommendations of the advisory committee on immunization practices for use of a hepatitis B vaccine with a novel adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67(15):455–458.
