Supplementary Data Search Strategy (Measles Vaccine / Ad

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Supplementary data

Search strategy

(Measles Vaccine / ad [Administration & Dosage] OR Measles Vaccine / im [Immunology]

OR Mumps Vaccine / ad [Administration & Dosage] OR Mumps Vaccine / im [Immunology]

OR Rubella Vaccine / ad [Administration & Dosage] OR Rubella Vaccine / im

[Immunology] OR Chickenpox Vaccine / ad [Administration & Dosage] OR Yellow fever

Vaccine / ad [Administration & Dosage] OR Yellow Fever Vaccine / im [Immunology] OR

Japanese encephalitis vaccine/ad [Administration & Dosage] OR Japanese encephalitis

vaccine/im [Immunology] OR BCG Vaccine / ad [Administration & Dosage] OR BCG

Vaccine / im [Immunology] OR Smallpox Vaccine / ad [Administration & Dosage] OR

Smallpox Vaccine / im [Immunology] OR Poliovirus Vaccine Oral / ad [Administration &

Dosage] OR Poliovirus Vaccine Oral / im [Immunology] OR Cholera Vaccines / ad

[Administration & Dosage] OR Cholera Vaccines / im [Immunology] OR Typhoid Vaccine /

ad [Administration & Dosage] OR Typhoid Vaccine / im [Immunology] OR Rotavirus

Vaccine / ad [Administration & Dosage] OR Rotavirus Vaccine / im [Immunology]) AND

(interval OR co-administration OR concomitant OR interference OR Drug Combinations / ad

[Administration & Dosage] OR Immunization Schedule OR Drug Administration schedule

OR Drug Interactions/im [Immunology] OR antibodies, viral OR antibodies, bacterial).

Results

Four studies investigated the effect of consecutive administration of MMR and varicella

vaccines.1-4 All four compared the administration of the vaccines either on the same day or

separated by 42 days. Three of the studies reported lower geometric mean antibody

concentrations (GMCs) and one lower seroconversion rates (SCRs) to varicella when MMR

Zimmermann P, et al. Arch Dis Child 2020;0:1–4. doi: 10.1136/archdischild-2020-320091 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Arch Dis Child

was given simultaneously with a varicella vaccine (administered separately or in one

vaccine).2-4 One study reported higher GMCs for measles4 and one study reported lower

SCRs for measles when MMR and varicella vaccines were given on the same day.3 In two

studies, GMCs and SCRs were similar for measles, mumps and rubella regardless of whether

the vaccines were given simultaneously or 42 days apart.1-4

Four studies investigated the effect of consecutive administration of a yellow fever vaccine

(YFV) and a measles-containing vaccine (MCV).5-8 One study investigated a time interval of

7 and 28 days,6 two studies different intervals between 1 and 27 days (compared with more

than 28 days),5, 8 and one study an interval of more than 30 days between the two vaccines.7

Two of the four studies reported lower GMCs and SCRs for YF when a MCV was given

simultaneously with the YFV.5, 7 Additionally, one study also reported lower SCRs for

rubella and mumps when the two vaccines were given simultaneously.7 In contrast, none, of

the studies reported an interaction between the two vaccines when they were given between 1

and 28 days apart.5, 6, 8

One study which investigated the effect of consecutive administration of an oral polio

vaccine (OPV) and a measles vaccine (MV).9 The study reported that when a MV was given

within 28 days of an OPV, SCRs to measles were not influenced.9

Three studies compared consecutive administration of OPV and an oral rotavirus vaccine

(ORV) with separate administration at intervals between 14 and 28 days.10-12 Compared with

simultaneous administration, giving the vaccines separately led to higher responses in two of

the three studies: one study found higher GMCs (immunoglobulin A and G) to rotavirus11

and one to polio type 2,10 while SCR to both vaccines were not influenced in either study. In

contrast, the third study found lower SCR for ORV when the vaccines were given 21 days

apart.12

Two studies investigated the potential interference between cholera vaccine (CV) and YFV.9,

13 The first study found that when CV was given 28 days before YFV or simultaneously,

compared to YFV given alone, this led to lower GMCs and SCRs to YF one month after

vaccination.13 However, this effect was only transient as the difference did not persist two

months after vaccination. Similarly, in another study, no difference in YF antibody responses

was found when the vaccines were given simultaneously, 1 to 10 days or more than 10 days

apart.9

Two studies investigated the issue in the case of Japanese encephalitis vaccine (JEV) and

YFV.14, 15 One reported that when YFV was given 30 days after JEV it led to higher GMCs

and SCRs for YF when compared with simultaneous administration or when JEV was given

30 days after YFV.14 In contrast, the other study reported lower SCRs when a YFV was given

30 days after a JEV.15 Notably, this finding is likely explained by the JEV in both studies

using a YF antigen as a vector.

Supplementary table 1 Findings of studies that have investigated the interference on vaccine immunogenicity of two or more different live attenuated vaccines administered consecutively

Citation Study group Study type Outcome Key results of antibody responses (IgG unless otherwise stated) to live Age Level of evidence vaccines

Vaccines MMR vaccine and varicella (V) vaccine Englund et al1 101 healthy children Single-centre, GMCs and SCRs No differences for varicella, measles, mumps and rubella 15 to 24m double-blinded, 42d after vaccination USA placebo-controlled, Group 1 (47): V (ns, Merck) simultaneously with MMR (M-M-R randomised study 1998 II® Merck) (1b) Group 2 (54): Placebo simultaneously with MMR; V 42d later

Shinefield et al2 444 healthy children Single-centre, non- GMCs and SCRs V simultaneously with MMR 12 to 23m blinded, controlled, 42 and 365d after • lower GMCs for varicella (10.5 vs 14.5 ELISA units, p-value ns) USA randomised study vaccination • lower SCRs for varicella (83 vs 91%, p-value ns) Group 1 (221): V (VARIVAX® Merck) simultaneously with (1b)

1998 MMR (M-M-R II® Merck) and DTPa-Hib (TETRAMUNE®) Group 2 (223): MMR simultaneously with DTPa-Hib; V 42d later

White et al3 318 healthy children Multicentre, non- GMCs and SCRs MMRV 12 to 42m blinded, controlled, 42d after vaccination • lower GMCs for varicella (6.9 vs 11.9 ELISA units, p<0.001) USA randomised study • lower SCRs for measles (96 vs 100%, p=0.03) Group 1 (160): MMRV(Merck) simultaneously with DTPa (1b) 1997 (ACEL-IMUNE® Lederle) and OPV (ORIMUNE® Lederle) Group 2 (158): MMR, DTPa and OPV; V 42d later

Reuman et al4 294 healthy children Multicentre, non- GMCs and SCRs MMRV 12 to 18m blinded, controlled, 42 and 365d after • lower GMCs for varicella (8.3 vs 11.7 ELISA units, p=0.03) USA randomised study vaccination • higher GMCs for measles (126.5 vs 90.9 ELISA units, p=0.004) Group 1 (147): MMRV (Merck) and Hib (PedvacHIB® Merck) (1b) 1997 simultaneously Group 2 (147): MMR (M-M-R II® Merck) and Hib; V 42d later

Measles-containing vaccine (MCV) and yellow fever vaccine (YFV) Goujon et al5 131 healthy children Multicentre, GMCs and SCRs YFV simultaneously with MCV 6 to 24m retrospective case- time ns • lower SCRs for YF (92 vs 100%, p-value ns) France control study (3b) Group 1 (62): MCV (M-M-RvaxPro® Sanofi Pasteur MSD or GMCs against YF and MMR increased as the time between immunisation 2017 Priorix® GlaxoSmithKline or Rouvax® Sanofi Pasteur MSD) increased simultaneously with YFV (Stamaril® Sanofi Pasteur MSD) Group 2 (50): MCV; YFV 1-27d later Group 3 (19): MCV; YFV >28d later

Michel et al6 258 healthy children Multicentre, GMCs and SCRs No differences for YF 9 to 14m prospective 28 to 60d after vaccination Senegal observational study French Guiana Group 1 (49): YFV (Stamaril® Sanofi Pasteur MSD or Vaccin (4) Amaril Stabilise® Institut Pasteur) simultaneously with MCV 2015

(M-M-RvaxPro® Sanofi Pasteur MSD or Priorix® GlaxoSmithKline or Rouvax® Sanofi Pasteur MSD) Group 2 (209): MCV; YFV 7-28d later

Nascimento et al7 1691 healthy children Multicentre, non- GMCs and SCRs YFV simultaneously with MMR 12 to 23m blinded, controlled, 30d after vaccination • lower GMCs against YF (1065 vs 3385 mIU/ml, p<0.001) Brazil randomised study • lower GMCs against rubella (25 vs 60 IU/ml, p<0.001) Group 1 (839): YFV (17DD or WHO-17D-213 substrains) (1b) • lower SCRs for YF (70 vs 88%, p<0.001) 2011 simultaneously with MMR (MMRI® Sanofi Pasteur MSD or Vacina combinada contra rubéola, sarampo e caxumbaTM • lower SCRs for rubella (90 vs 97%, p<0.001) GlaxoSmithKline) • lower SCRs for mumps (61 vs 71%, p<0.001) Group 2 (852): MMR; YFV >30d later GMCs against YF and rubella increased as the time between immunisation increased

Stefano et al8 294 healthy children Multicentre, non- GMCs and SCRs No differences for YF 9m blinded, controlled, >42d after vaccination Brazil randomised study Group 1 (57): MCV (Schwarz strain, Merieux or Sclavo); YFV (1b) 1999 (strain 17DD) 1-6d later Group 2 (53): MCV; YFV 7-13d later Group 3 (65): MCV; YFV 14-21d later Group 4 (54): MCV; YFV 22-27d later Group 5 (65): MCV; YFV >28d later

Measles vaccine (MV) and oral polio vaccine (OPV) Pannuti et al16 205 healthy children Multicentre, SCRs No differences for measles 9m prospective 14-19d after vaccination Brazil observational study for children with MV <28d Group 1 (23): MV (BIKEN CAM 70); OPV (Sabin) 2-6d later (4) after OPV and >20d after 1987 Group 2 (37): MV; OPV 9-13d later vaccination for children Group 3 (42): MV; OPV 16-20d later with MV >28d after OPV Group 4 (15): MV; OPV 23-26d later Group 5 (88): MV; OPV >28d later

Oral polio vaccine (OPV) and oral rotavirus vaccine (ORV) Zaman et al10 200 healthy infants Single-centre, non- GMCs and SCRs (IgA) OPV simultaneously with ORV 10w blinded, controlled, 30d after vaccination • higher GMCs for polio type 2 (839 vs 455 U/ml, p-value ns) Bangladesch randomised study Group 1 (100): OPV (Polio Sabin® GSK Biologicals) (1b) 2009 simultaneously with ORV (Rotarix® GSK Biologicals) (2 doses 28d apart) Group 2 (100): OPV with DTPw-HepB; ORV 15d later (2 doses 28d apart)

Both groups received OPV with DTPw-HepB at 42d

Ciarlet et al11 694 healthy infants Multicentre, non- GMCs and SCRs OPV simultaneously with ORV 6 to 12w blinded, controlled, 42d after vaccination • lower GMCs for IgA (155 vs 293 U/ml, p-value ns) and ORV neutralizing Mexico randomised study IgGs (G1 126 vs 183, P1A 85 vs 131, p-value ns) but not for others (G2 27 Costa Rica Group 1 (368): ORV (G1-G4, P1) simultaneously with OPV (1b) vs 30, G3 21 vs 23, G4 59 vs 75, p-value ns) Guatemala (Polio Sabin® Sanofi Pasteur or BIRMEX) (3 doses 57-70d Brazil apart) Group 2 (326): ORV; OPV 14-28d later (3 doses 42d apart) 2008

Jalil et al12 49 healthy infants Single-centre, SCRs 21d after ORV OPV simultaneously with ORV 6w prospective SPRs 42d after ORV • higher SCRs for ORV (18 vs 9%, p-value ns) Pakistan observational study Group 1 (25): ORV (MMU-18006) simultaneously with OPV (4) 1991 (Virelonf® Behring); OPV 42d and 84d later, DTP 15w later Group 2 (24): ORV with DTP; OPV 21d later; OPV + DTP 42d and 84d later

Cholera vaccine (CV) and Japanese encephalitis vaccine (JEV) Poveda et al9 121 healthy adults Single-centre, GMCs and SCRs No differences for YF Age ns retrospective, case- 47 ± 40m after JEV France control study (3b) Group 1 (30): CV (ns) simultaneously with JEV (Amaril 17 D 1990 Rockefeller) Group 2 (26): CV; JEV 1-10d later Group 3 (28): JEV; CV 1-10d later Group 4 (17): CV; JEV >10d later or JEV, CV >10d later Group 5 (20): JEV only

Gateff et al13 471 healthy children Single-centre, GMCs and SCRs CV simultaneously with JEV vs JEV alone 2 to 5y prospective, case- 30d after vaccination • lower GMCs for JE (8.7 vs 16.7 units, p-value ns) Cameroun control study (3b) • lower SCRs for JE (99 vs 70%, p-value ns) Group 1 (60): CV (serotype Ogawa, Institut Pasteur de Paris) 1973 simultaneously with JEV (Amaril 17 D Rockefeller, Institut CV 28d before JEV vs JEV alone Pasteur de Dakar) Group 2 (95): CV; JEV 28d later • lower GMCs for JE (13.2 vs 16.7 units, p-value ns) Group 3 (69): CV (2 doses one week apart); JEV 28d later • lower SCRs for JE (99 vs 95%, p-value ns) Group 4 (69): JEV; CV 28d later Group 5 (70): JEV only CV 28d (2 doses with a one-week interval) before JEV vs JEV alone Group 6 (108): CV only • lower GMCs for JE (11.7 vs 16.7 units, p-value ns) • lower SCRs for JE (99 vs 96.5%, p-value ns)

154 healthy children GMCs and SCRs No differences for JE 2 to 5y 60d after vaccination

Group 1 (82): CV (serotype Ogawa, Institut Pasteur de Paris) simultaneously with JEV (Amaril 17 D Rockefeller, Institut Pasteur de Dakar)

Group 2 (72): JEV only

Japanese encephalitis vaccine (JEV) and yellow fever vaccine (YFV) Nasveld et al14 108 healthy adults Single-centre, GMCs and SCRs YFV 30d after JEV vs JEV followed by YFV 30d later 18 to 53y double-blinded, 30d after JEV • higher GMCs for JE (1500 vs 400 units, p-value ns) Australia placebo-controlled

Group 1 (18): JEV (ChimerixVax-JE® Sanofi Pasteur) randomised study • higher SCRs for JE (100 vs 91%, p-value ns) 2010 simultaneously with YFV (Stamaril® Sanofi Pasteur MSD); (1b) placebo 30d later YFV 30d after JEV vs JEV simultaneously with YFV Group 1 (18): placebo; JEV simultaneously with YFV 30d later • higher GMCs for JE (1500 vs 150 units, p-value ns) Group 2 (36): JEV; YFV 30d later Group 3 (36): YFV; JEV 30d later • higher SCRs for JE (100 vs 96%, p-value ns)

Monath et al15 22 healthy adults Single-centre, SCRs 30d after YFV 30d after JEV 18 to 58y double-blinded, vaccination • lower SCRs for JE (64 vs 91%, p-value ns) USA controlled Group 1 (11): JEV (ChimerixVax-JE® Sanofi Pasteur); YFV randomised study 2003 (JE-VAX®, Aventis-Pasteur) 30d later (1b) Group 2 (11): YFV; JEV 30d later

CV – cholera vaccine d – days DTPa-Hib – diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b GMC – geometric mean antibody concentration Hib – Haemophilus influenzae type b vaccine Ig – immunoglobulin JEV – Japanese encephalitis vaccine m – months MCV – measles-containing vaccine MMR – measles-mumps-rubella vaccine MMRV – measles-mumps-rubella-varicella vaccine MV – measles vaccine ns – not specified OPV – oral polio vaccine ORV – oral rotavirus vaccine SCR – seroconversion rates SPR – seroprotection rates w – weeks V – varicella y – years YFV – yellow fever vaccine

1. Englund JA, Suarez CS, Kelly J, Tate DY, Balfour HH, Jr. Placebo-controlled trial of varicella vaccine given with or after measles-mumps-rubella vaccine. J Pediatr. 1989;114(1):37-44. 2. Shinefield HR, Black SB, Staehle BO, Adelman T, Ensor K, Ngai A, et al. Safety, tolerability and immunogenicity of concomitant injections in separate locations of M- M-R II, VARIVAX and TETRAMUNE in healthy children vs. concomitant injections of M-M-R II and TETRAMUNE followed six weeks later by VARIVAX. Pediatr Infect Dis J. 1998;17(11):980-985. 3. White CJ, Stinson D, Staehle B, Cho I, Matthews H, Ngai A, et al. Measles, mumps, rubella, and varicella combination vaccine: safety and immunogenicity alone and in combination with other vaccines given to children. Measles, Mumps, Rubella, Varicella Vaccine Study Group. Clin Infect Dis. 1997;24(5):925-931. 4. Reuman PD, Sawyer MH, Kuter BJ, Matthews H. Safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine and PedvaxHIB vaccines in healthy children twelve to eighteen months old. The MMRV Study Group. Pediatr Infect Dis J. 1997;16(7):662-667. 5. Goujon C, Gougeon ML, Tondeur L, Poirier B, Seffer V, Despres P, et al. CHRONOVAC VOYAGEUR: A study of the immune response to yellow fever vaccine among infants previously immunized against measles. Vaccine. 2017;35(45):6166-6171. 6. Michel R, Berger F, Ravelonarivo J, Dussart P, Dia M, Nacher M, et al. Observational study on immune response to yellow fever and measles vaccines in 9 to 15-month old children. Is it necessary to wait 4 weeks between two live attenuated vaccines? Vaccine. 2015;33(20):2301-2306. 7. Nascimento Silva JR, Camacho LA, Siqueira MM, Freire Mde S, Castro YP, Maia Mde L, et al. Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella. Vaccine. 2011;29(37):6327-6334. 8. Stefano I, Sato HK, Pannuti CS, Omoto TM, Mann G, Freire MS, et al. Recent immunization against measles does not interfere with the sero-response to yellow fever vaccine. Vaccine. 1999;17(9-10):1042-1046. 9. Poveda JD, Raccurt CP, Le Fur R, M'Bailara L, Malvy JM, Le Bras M, et al. [The inhibiting effect of anticholera vaccination carried out simultaneously or at short intervals on yellow fever immunization. Is it real or assumed? Results of a retrospective study]. Bulletin de la Societe de pathologie exotique (1990). 1990;83(4):529-535; discussion 535-526. 10. Zaman K, Sack DA, Yunus M, Arifeen SE, Podder G, Azim T, et al. Successful co- administration of a human rotavirus and oral poliovirus vaccines in Bangladeshi infants in a 2-dose schedule at 12 and 16 weeks of age. Vaccine. 2009;27(9):1333- 1339. 11. Ciarlet M, Sani-Grosso R, Yuan G, Liu GF, Heaton PM, Gottesdiener KM, et al. Concomitant use of the oral pentavalent human-bovine reassortant rotavirus vaccine and oral poliovirus vaccine. Pediatr Infect Dis J. 2008;27(10):874-880. 12. Jalil F, Zaman S, Carlsson B, Glass RI, Kapikian AZ, Mellander L, et al. Immunogenicity and reactogenicity of rhesus rotavirus vaccine given in combination with oral or inactivated poliovirus vaccines and diphtheria-tetanus-pertussis vaccine. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1991;85(2):292- 296.

13. Gateff C, Le Gonidec G, Boche R, Sarrat P, Lemarinier G, Monchicourt D, et al. [Effect of anticholera vaccination on associated anti-yellow fever immunization]. Bull Soc Pathol Exot Filiales. 1973;66(2):258-266. 14. Nasveld PE, Marjason J, Bennett S, Aaskov J, Elliott S, McCarthy K, et al. Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: randomized double-blind phase II evaluation of safety and immunogenicity. Hum Vaccin. 2010;6(11):906-914. 15. Monath TP, Guirakhoo F, Nichols R, Yoksan S, Schrader R, Murphy C, et al. Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen. The Journal of infectious diseases. 2003;188(8):1213-1230. 16. Pannuti CS, de Souza VA, Takaoka N, da Silva Leme ST, Pereira CR, de Souza Carvalho RP, et al. [Interference between measles and poliomyelitis vaccines]. Bol Oficina Sanit Panam. 1987;103(3):227-232.

Zimmermann P, et al. Arch Dis Child 2020;0:1–4. doi: 10.1136/archdischild-2020-320091