Protecting people with multiplesclerosis through vaccination

Saúl Reyes ,1,2 Mary Ramsay,3 Shamez Ladhani,3

Gayatri Amirthalingam,3 Neena Singh,2 Carlos Cores,1 joela Mathews,4

Jonathan Lambourne,5 Monica Marta ,1,2 Benjamin Turner ,2

Sharmilee Gnanapavan,1,2 Ruth Dobson ,2,6 Klaus Schmierer ,1,2

G Giovannoni 1,2

ABSTRACTVaccination is one of the most effective and cost-efficient methods for protecting people withmultiple sclerosis (MS) from infections. However,use of vaccines has often been problematicbecause of misguided concerns that they mayexacerbate the disease and/or that some disease-modifying therapies may influence the immuneresponse to immunisations and/or their safety.People with MS risk higher morbidity andmortality from vaccine-preventable infections. Itis, therefore, important to address any patient’sreluctance to accept vaccination and to provideclear guidance for clinicians on which vaccinationsto consider proactively. We have reviewed thecurrent literature and provide recommendationsregarding vaccines in adults with MS, includingspecific advice regarding vaccination safety inpatients receiving—or going to receive—disease-modifying therapies, vaccination duringpregnancy, pretravel counselling and patienteducation.

INTRODUCTIONImmunisation through vaccination is oneof the most cost-effective tools for pre-venting potentially serious and life-threatening infectious diseases. Recentoutbreaks of vaccine-preventable infec-tions in countries where these infectionshad been considered eliminated havedrawn attention to the implications ofa declining vaccine coverage worldwide.1

Factors affecting vaccine uptake includeparental or patient reluctance to vaccinate(‘vaccine hesitancy’), difficulty in acces-sing immunisation services and failure ofhealthcare professionals to offer and pro-mote appropriate vaccination correctly.1

False contraindications to vaccinationwere a known cause of under-vaccinationin the 1980s,2 but for the healthy popula-tion have been largely mitigated by the

ready availability of authoritative advice,such as the UK’s Immunisation AgainstInfectious Disease (the ‘Green Book’).3

Research into public confidence in vac-cination concludes that it is currently highin the UK, and most people trust respec-tive advice from healthcare professionals.4

Nevertheless, coverage in England hasdeclined for all vaccinations routinelygiven to children in 2018–2019 comparedto previous years.5 A report fromNationalHealth Service (NHS) Digital showed thatcoverage of the measles, mumps andrubella (MMR) vaccine for children reach-ing 2 years of age fell for the fifthsuccessive year. Uptake was 90.3% inEngland in 2018–2019, down from91.2% in 2017–2018 and the lowestlevel since 2010–2011.5 In 2018, therewere 913 laboratory-confirmed cases ofmeasles in England. Adults aged 15 yearsand over who missed their MMR vaccinein childhood have been particularlyaffected.6

As adults are also at risk of acquiringvaccine-preventable infections, eitherbecause of incomplete immunisation orwaning immunity, vaccination may berecommended throughout life and somevaccines may be specifically targeted tothose with underlying medicalconditions.3 However, immunisation cov-erage in at-risk adults remains low formost routinely recommended vaccines.Although influenza vaccination coveragefor the UK population aged over 65 yearsremains above 70%, coverage in indivi-duals aged less than 65 years in clinicalrisk groups remains suboptimal and isonly 50.3% in those with neurologicalconditions.7 Similarly, vaccine coveragefor shingles prevention in England hasdeclined more than 15% since the pro-gramme began in 2013.8 Logistical

1Neuroscience and Trauma,Blizard Institute of Cell andMolecular Science, London, UK2Department of Neurology, RoyalLondon Hospital, Barts HealthNHS Trust, London, UK3Immunisation andCountermeasures Division, PublicHealth England, London, UK4Pharmacy Service, Barts HealthNHS Trust, London, UK5Department of Microbiology andInfectious Diseases, Barts HealthNHS Trust, London, UK6Preventive Neurology Unit,Wolfson Institute of PreventiveMedicine, London, UK

Correspondence toSaúl Reyes, Blizard Institute,Barts and the London School ofMedicine and Dentistry, QueenMary University of London, 4Newark St, Whitechapel,London E1 2AT, UK; saul.reyes@nhs.net

Accepted 26 May 2020

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© Author(s) (or theiremployer(s)) 2020. Nocommercial re-use. See rightsand permissions. Published byBMJ.

To cite: Reyes S, Ramsay M,Ladhani S, et al. Pract Neurol2020;20:435–445.

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http://orcid.org/0000-0002-3230-3263http://orcid.org/0000-0002-5464-9070http://orcid.org/0000-0002-7537-2357http://orcid.org/0000-0002-2993-585Xhttp://orcid.org/0000-0002-9293-8893http://orcid.org/0000-0001-9995-1700mailto:saul.reyes@nhs.netmailto:saul.reyes@nhs.nethttp://pn.bmj.comhttp://crossmark.crossref.org/dialog/?doi=10.1136/practneurol-2020-002527&domain=pdfhttp://pn.bmj.com/

challenges that may have contributed to this trendinclude issues around eligibility criteria, attempting togive the vaccine at the same visit as the influenza vac-cine, and difficulties identifying those inwhom the live-attenuated vaccine is contraindicated.8

Apart from the risks to unvaccinated individuals,declining vaccine coverage in the population has poten-tially serious implications for at-risk groups such aspeople with multiple sclerosis (MS). It is, therefore,very important that people withMS (and their relativesor contacts) undergo an appropriate vaccinationprogramme.

VACCINATION AND MSHistorical observations of postvaccination encephalo-myelitis or the onset/relapse of other demyelinatingillnesses following vaccination have contributed todamaging controversies in vaccine safety9; case reportsof patients developingMS following hepatitis B vaccinecaused concern in the 1990s.10 However, in the pasttwo decades, multiple studies have shown the absenceof a causal link between vaccination and the onset orrelapse of MS. The available evidence suggests thathepatitis B, human papillomavirus, influenza, tetanus,diphtheria, pertussis, polio, BCG, typhoid, tick-borneencephalitis or MMR vaccinations do not increase therisk of developing MS.11–15 Similarly, several studieshave found no increased risk of MS exacerbation fol-lowing hepatitis B, tetanus, tick-borne encephalitis orinfluenza vaccinations.11–13 16 17 One possible excep-tion, despite relatively little evidence, is the live-attenuated vaccine against yellow fever, where a caseseries showed relapses in 5/7 people withMS soon afterreceiving this.18 However, this report has been criti-cised for methodological issues.19 More recently,a small retrospective study reported that yellow fevervaccination was associated with neither an increase inMS relapses nor emergence of brain and/or spinal cordlesions.20 These contrasting results could relate to dif-ferences in the efficacy profile of disease-modifyingtherapies used soon after yellow fever vaccination andwe need further research to establish or exclude anypotential causal association.20

Although there is no compelling evidence that vac-cines increase the risk of relapse in MS, some expertsremain concerned that vaccination may worsen relapseseverity in people with MS who are actively experien-cing a relapse.17 Vaccination in routine MS clinicalpractice is typically non-urgent (ie, a delay of a fewweeks would not significantly increase the risk of anyvaccine-preventable disease), and so immunisation ofpeople with MS experiencing a relapse should bedeferred until clinical resolution or until the relapse isno longer active/progressive.17

In people withMS not receiving immunotherapy, thebenefits of most vaccines greatly outweigh any poten-tial risks. These people should be capable of mounting

an immune response to antigenic stimulation similar tothose who do not have MS.21 A disease-related influ-ence on vaccination response is unlikely in the light ofrecent studies showing that interferon-treated patientshave similar seroconversion rates to influenza vaccinecompared to healthy controls.22–25 People with MSshould have their vaccination status reviewed andupdated as soon as possible after establishing theirdiagnosis of MS to prevent future delays in startingimmunotherapies.17

High immunisation rates within a community protectnot only the people who are vaccinated but also vulner-able individuals via herd (indirect or population)immunity, including immunocompromised adults whocannot be immunised with live vaccines and who maybe less well protected by the other vaccines that theycan receive.26 Those with MS exposed to immunosup-pressive therapies and those with worse disability arenot only more susceptible to infection but also riskhigher morbidity and mortality from many vaccine-preventable infections.27 28 Additionally, MS exacerba-tions associated with infections may lead to moresevere and sustained neurological deficit than sponta-neous relapses.29–31

Table 1 summarises some of the current vaccinesavailable to adults (either privately or on the NHS)and our recommendations about their administrationin people with MS.3 32 These recommendations are inline with the national immunisation programme.33

Additional information for each vaccine is availablevia the ‘electronic medicines compendium’ and shouldbe consulted for specific information relating to theseproducts.32

Disease-modifying therapies for MS may influencethe immune response against vaccines and their safety.Although there are no major concerns about vaccina-tion in people with MS treated with interferon β pre-parations, this is not the case with newer disease-modifying therapies.34 Everyone with MS who isimmunocompromised or being considered for immu-notherapy needs their vaccination history assessedcarefully and to have a plan made for future vaccina-tions. The optimal timing for any vaccination should bebased upon a judgement about the relative need forrapid protection and the likely response tovaccination.3

Inactivated vaccines should ideally be given at least 2weeks before starting maintenance immunosuppressiveand immune reconstitution therapies (ie, short coursetherapies resulting in long-term qualitative changes inimmune function, such as alemtuzumab andcladribine).3 35 A recent study showed that peoplewith MS treated with ocrelizumab had an attenuatedhumoral response to tetanus, pneumococcus and sea-sonal influenza vaccination, compared to thoseexposed to interferon β or no therapy.36 Although thisfinding supports current recommendations that peoplewith MS ideally receive inactivated vaccines before

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starting immunosuppressive therapies, it also suggeststhat seasonal vaccinations such as the inactivated influ-enza vaccine have a favourable safety profile and willstill provide some protection in patients already receiv-ing these disease-modifying therapies.34 36 Whenimmunisation with inactivated vaccines is not possiblebefore starting treatment, inactivated vaccines can begiven at any time, with re-immunisation consideredafter treatment is stopped/finished and the immunesystem has recovered/reconstituted (ie, resolution oflymphopenia, adequate antibody responses to vaccinesand no increased risk of immunosuppression-relatedcomplications, such as opportunistic infections andsecondary malignancies).3 35

Due to the risk of vaccine-transmitted disease, live-attenuated virus vaccines such as MMR, varicella-zoster virus (VZV) and yellow fever vaccines are gen-erally not recommended in people with MS during andshortly (

antigens previously met) after alemtuzumabtreatment.41 In contrast, most haematopoietic stem-cell transplant recipients lose specific humoral immu-nity 1 year after transplantation and should be con-sidered as never vaccinated.38 Therefore, people withMS receiving a haematopoietic stem-cell transplantshould be considered for a re-immunisation pro-gramme after transplantation. Table 2 summarisesthese and other vaccination recommendations for dis-ease-modifying therapies.Live vaccines should not be given to people with MS

who for any reason are receiving or have received in thepast 3 months high-dose corticosteroids (ie, >40 mg/day of prednisone or equivalent for ≥7 consecutivedays OR >20 mg/day of prednisone or equivalent for≥14 consecutive days).3 Although inactivated vaccinesmay be given to people taking high-dose corticoster-oids, they may elicit a lower response than in immuno-competent individuals.3

SPECIFIC ADVICE REGARDING INDIVIDUALVACCINESInfluenza vaccineIn the UK, the influenza vaccine is available each year toprotect against the strains of influenza that areexpected to circulate in the coming season.3 ThePublic Health England routine immunisation scheduleguideline states that adults with chronic neurologicalconditions, such as MS, and/or those who are immuno-suppressed due to disease or treatment should receivethe influenza vaccine (table 1).33 Influenza immunisa-tion should also be recommended for household mem-bers and carers of people withMS, as well as healthcareprofessionals with face-to-face duties managing peoplewith MS.3

Every year, up to 650 000 people die from complica-tions of seasonal influenza worldwide.50 We recentlyhad a fatal case of influenza A pneumonia in a disabledperson with MS who developed grade 4 lymphopeniaafter receiving off-label subcutaneous cladribine.Unfortunately, this patient had not had the influenzavaccine despite its wide availability on the NHS.Whether or not this patient would have been protectedby this vaccine is unknown. Notably, there have not yetbeen any published formal vaccine trials in people withMS receiving cladribine. However, as the trivalent andquadrivalent inactivated influenza vaccines can gener-ally be considered safe at any point of treatment and arelikely to provide some protection, we recommendannual influenza vaccination with inactivated but notlive vaccines, in immunocompromised people withMS.The live-attenuated influenza vaccine is given as

a nasal spray and is only licensed for children andyoung people aged

currently offered using Varivax/Varilrix live-attenuatedvaccines; adults should receive two doses at least4 weeks apart.3 32 For protection against herpes zoster

(shingles) and related complications in older people inthe UK, since September 2013, Zostavax (a live-attenuated vaccine) is routinely offered to

Table 2 Vaccination and disease-modifying therapiesClass Vaccination Comments

Interferonβ22–25 42 43 Maintenance immunomodulatory Safe and effective -

Glatiramer acetate22 35 Maintenance immunomodulatory Safe. Inactivated influenza vaccine may be lesseffective

-

Teriflunomide32 44 45 Maintenance immunomodulatory Inactivated neoantigens (first vaccination) and recallantigens (re-exposure) have been found to be safeand effective.Live-attenuated vaccines should be avoided duringtreatment and for 6 months after stopping (SmPCrecommendation)

The long half-life of teriflunomide should beconsidered (unless an accelerated eliminationprotocol is used) when contemplating vaccinationwith live-attenuated vaccines after stoppingteriflunomide

Dimethyl fumarate32 43 Maintenance immunosuppressive Inactivated neoantigens and recall antigens havebeen found to be safe and effective.Live-attenuated vaccines should be avoided untillymphocyte counts have returned to above 800/mm3

after stopping treatment

MMR screening before starting treatment.*VZV screening is also advisable given the potentialrisk of persistent lymphopenia (

immunocompetent people aged 70 years.3 A catch-upprogramme has also been underway since 2013 forindividuals aged 71–79 years, based on evidence ofcost-effectiveness (table 1).55 In the USA, Shingrix (arecombinant vaccine) is recommended for adults aged50 years and older.56 The UK Joint Committee onVaccination and Immunisation has recommended thatShingrix should be offered to adults aged 60–70 years,immunocompromised people who are eligible in thecurrent programme but contraindicated for immunisa-tion with Zostavax and immunocompromised peopleaged 50 years and older.8 Shingrix, however, is notcurrently available under the NHS.VZV vaccines can be given at the same time as poly-

saccharide pneumococcal and inactivated influenzavaccines.57 58 Responses to varicella and MMR vac-cines are adequate when the vaccines are successfullyco-administered on the same day. However, the inter-feron production stimulated by the replication of a firstvaccine virus may prevent the replication of a secondagent when these live vaccines are not administeredsimultaneously.3 Where any vaccine is required rapidlythen they can be administered at any interval, but anadditional dose of the vaccine given second should beconsidered at least 4 weeks later.3 Since this may delaystarting disease-modifying therapy, the potential risksand benefits must be considered on a case-by-case basis.

Human papillomavirus vaccineHuman papillomavirus is responsible for 99.7% ofcases of cervical cancer and is also strongly associatedwith the development of other anogenital and orophar-yngeal cancers.59 A major reason to vaccinate peoplewith MS is that immunosuppression is associated withan increased risk of these virus-associatedmalignancies.60 From 2019, routine vaccination willbe offered to all girls and boys aged 12–13 years whenthey are in school year 8. The current vaccine offered isGardasil, which protects against human papillomavirustypes 6, 11, 16 and 18. These four types cover about70% of cervical cancers in the UK.61 The newer poly-valent vaccine, Gardasil 9, protects against humanpapillomavirus 6, 11, 16, 18, 31, 33, 45, 52 and 58and covers over 90% of cervical cancers but is not yetavailable through the national programme (table 1).62

Human papillomavirus vaccines are highly effectivein protecting against cervical cancer in adolescents andyoung women before they acquire natural humanpapillomavirus infection.63 Unvaccinated individualscurrently remain eligible for vaccination on the NHSuntil they reach 25 years of age. Vaccinating men andwomen older than 25 years, and those who havealready been infected, may also reduce their chancesof developing precancerous lesions and can be offeredoutside of the national programme at the discretion ofthe clinician.3 63 A 3-dose schedule (0, 1–2 and6 months) over a period of maximum 12 months

should be used if immunisation is started at age 15,64

which will delay starting continuous immunosuppres-sive therapies for more than 6 months (at least 2 weeksafter the last dose). In the case of some immune recon-stitution therapies (cladribine and alemtuzumab), theinitial two doses could be given (0 and 1–2 months)before starting such treatments and the third dose afterthe immune system reconstitution (months 9–11).A recent study in the US showed that just one dose ofhuman papillomavirus vaccine is associated witha significant reduction in cervical disease.65 In clinicalpractice, physicians and people with MS must decideon whether the potential benefit of human papilloma-virus vaccination outweighs the risks of delaying treat-ment at the individual patient level. Vaccination againsthuman papillomavirus should be particularly consid-ered before starting fingolimod, and other emergingsphingosine-1-phosphate–receptor modulators, whichmay result in impaired intrinsic cancerimmunosurveillance.66 A link between fingolimodand human papillomavirus-driven conditions has beenrecently highlighted by a report of chronic and treat-ment-refractory cutaneous and genital warts in peoplewith MS treated with fingolimod.67

Although ideally the human papillomavirus vaccineshould be given before people become immunocom-promised, this vaccination is safe and likely also tobenefit those with impaired immune responsiveness.60

Routine cervical/human papillomavirus screeningaccording to national guidelines is critical for allwomen with MS, regardless of their human papilloma-virus vaccination status.64 Women aged 25–49 yearsare invited every 3 years, whereas those aged 50–64years are invited every 5 years.3

MMR vaccineGiven the recent increase in measles virus circulation inEngland, we have started to screen our patients withMS for previous MMR vaccination, before startingmaintenance immunosuppressive or immune reconsti-tution therapies (table 2). People with MS who missedone MMR vaccination when they were younger maynot be immune. Patients without a reliable history ofappropriate immunisation (ie, having received twodoses of MMR) are tested for measles and rubella anti-bodies and, if not immune, we recommend MMR vac-cination, which can be provided on the NHS (table 1).3

Our aim is to de-risk MS treatments because measles isa highly contagious virus and measles inclusion bodyencephalitis, for example, results in neurological dete-rioration and death in people with impaired cellularimmunity within months of the acute illness.68

Although over 99% of persons who receive two dosesof MMR vaccine develop measles antibodies, waningmeasles immunity occurs in approximately 5% of caseswithin 10–15 years after vaccination.69 However,measles infection in those with pre-existing immunity

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is generally less severe and less transmissible than infec-tion in unimmunised individuals.70

VACCINES DURING PREGNANCYAs MS is more commonly diagnosed in women thanmen, and during their childbearing years, considera-tion needs to be given to pregnant women with MStaking disease-modifying treatments. Pregnantwomen in the UK are routinely offered the inacti-vated influenza and the inactivated diphtheria, teta-nus and acellular pertussis (dTaP) vaccines, whileother vaccines may be considered in cases of highrisk or specific exposure.3 33 Due to changes insystemic immunity during pregnancy, morbidityand mortality rates associated with influenza arehigher in pregnant women, particularly inthe second and third trimesters.71 As such, womenwho are pregnant during the influenza season (fromSeptember to February) should be offered the inac-tivated influenza vaccine. It is safe to receive thisvaccine at any stage of an uncomplicatedpregnancy.72 The recommendations for the influ-enza vaccine in the context of disease-modifyingtreatments have been detailed in the previoussection.A pertussis-containing vaccine for pregnant

women arose as a recommendation following the2012 epidemic of pertussis in the UK, with 9300cases reported in England.73 A programme invol-ving the vaccination of pregnant women started inOctober 2012; such programmes also exist in theUS, Australia and some European countries.74 75

The vaccine should ideally be given at20–32 weeks gestation to allow optimal maternalantibody transfer across the placenta to help protectthe fetus and newborn against pertussis, but thevaccine can be given from as early as 16 weeksgestation.3 The vaccine currently offered in the UKis Boostrix-IPV, which is a combined dTaP and inac-tivated poliovirus vaccine (table 1). Pregnantwomen with MS should be vaccinated according tothe national recommendations described earlier. Thevaccine does not contain any live components and,as such, should be safe to administer to pregnantwomen with reduced immunocompetence, althoughthe vaccine response may be attenuated.32

TRAVEL VACCINATIONSInternational travellers may be at risk for variouspotentially severe and vaccine-preventable infectionsthat are absent or uncommon in their home terri-tories. People with MS who plan overseas travelshould undergo a risk assessment (based on theiritinerary, duration of stay and planned activities)and guidance on vaccination by a general practi-tioner or a travel clinic, ideally at least 6–8 weeksbefore travelling. Prevention should also focus onensuring safe food and water, good personal

hygiene, travel medications (such as malaria prophy-laxis) and precautions about avoiding being bittenby insect vectors.76 In addition, a pretravel consul-tation provides an opportunity to discuss not onlytravel vaccines but also all routinely recommendedvaccines.76 Figure 1 provides a simple guide to tra-vel immunisations (if indicated) for adults with MS,focusing on vaccines available in the UK.3 77 Thesafety and immunogenicity of inactivated and livevaccines in people with MS receiving immunother-apy should be carefully considered before theadministration of travel vaccines, and those withMS on such treatments should be advised to high-light these to their travel clinics. Travel vaccinesother than those shown in figure 1 may be requiredin some specific situations. TRAVAX and theNational Travel Health Network and Centre portal‘TravelHealthPro’ provide more detailed informa-tion on travel vaccines.3 77

PATIENT EDUCATIONVaccine hesitancy has been identified by the WHOas one of the top global threats in 2019.79 TheWHO’s Strategic Advisory Group of Experts onImmunisation has defined vaccine hesitancy as ‘adelay in acceptance or refusal of vaccines despiteavailability of vaccination services’.80 The factorsunderlying hesitancy are variable and differ byareas, cultures, communities, socioeconomic status,political inclinations, parental age, beliefs aboutsafety and effectiveness, and the availability of layadvice via online and social media resources.81 Theclaim linking the MMR vaccine with autism hasbeen a widely publicised example of misinforma-tion, which was difficult to rectify, not least due toits publication in a high-impact journal and despiteoverwhelming evidence refuting the claim.82

Addressing vaccine hesitancy is paramount in theage of administering immunosuppressive therapiesbecause of the increased risk of significant morbidityand mortality associated with infection in a patientwith reduced immunocompetence. We need strate-gies to manage vaccine hesitancy, particularly inthose with MS, to prevent delays in starting disease-modifying treatments. Redirection of patients totrusted, clinically verified online information sitesvia the WHO’s ‘Vaccine safety net’ initiative shouldbe encouraged. The UK has applied ‘TailoringImmunisation Programme’ methodologies createdby the WHO/Europe, for example, to theOrthodox Jewish Charedi community of NorthLondon.83 The Tailoring Immunisation Programmeis a framework that provides tools to identify lowvaccine coverage groups, diagnose supply-side anddemand-side immunisation barriers, identify motiva-tors to vaccination and create evidence-basedresponses to sustain vaccination.84

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The role of the general practitioner and other health-care professionals is key, because they are the mosttrusted sources of information on vaccination.4 Forpeople with chronic medical conditions, such as MS,recommendations for vaccinations at the appropriatetime by their clinical specialist will facilitate the processand help support both the patient and the primary careteam in ensuring that optimal protection is achievedagainst vaccine-preventable diseases. Routinely offer-ing vaccinations during regular health checks, and pro-viding information in local languages is also key topromoting vaccine uptake.83 84

CONCLUSIONAlthough vaccinations are safe and effective for thevast majority of people with MS, some specific con-siderations should be kept in mind when planning

vaccination strategies for them before, during andafter receiving immunotherapy. People with MS mayhave an increased risk of morbidity and mortalityfrom vaccine-preventable infections and, therefore,we must address their concerns with confidence.The aim has to be that we all, physicians and scien-tists, recognise the threat this poses and that,together with public health initiatives, we improvecurrent vaccine uptake overall and in people withMS, within our practices and communities. As pri-mary care physicians are among the most trustedadvisors and influencers of vaccine decisions, weshould support them in their mission to build con-fidence in the effectiveness and safety of vaccines.Community vaccination may be one of the mostcost-effective methods for protecting peoplewith MS.

Figure 1 Travel immunisations for adults with MS. *Combined hepatitis A/typhoid (ViATIM) and hepatitis A/hepatitis B (TwinrixAdult) vaccines are also available in the UK. **If more than 2 years have elapsed since the last vaccination, the primary course shouldbe repeated. ***The list of countries considered by the WHO to be infected with polio or vulnerable to it has been recently reviewedand is in the public domain.78 †Postexposure schedule depends on a risk assessment and the calculation of a composite rabies risk.‡A single dose of yellow fever vaccine appears to confer lifelong protective immunity against yellow fever disease. HAV, hepatitisA virus; IM, intramuscular; JEV, Japanese encephalitis virus; RV, rabies virus; SC, subcutaneous; TBEV, tick-borne encephalitis virus; Td,tetanus/diphtheria; YFV, yellow fever virus.

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Twitter G Giovannoni @gavingiovannoni.Acknowledgements We thank ECTRIMS (European Committeefor Treatment and Research in Multiple Sclerosis) for supportingSR through their MS clinical training fellowship programme. Wealso thank the National Travel Health Network and Centre(NaTHNaC) and its members for their input into thedevelopment of the travel immunisation recommendations.Contributors SR and GG conceived the review. SR, NS and GGwrote the first draft of the manuscript. All the authorsparticipated in the critical revision of the manuscript.Competing interests None declared.Patient consent for publication Not required.Ethical approval information Not applicable.Data sharing statement Not applicable.Provenance and peer review Not commissioned; externally peerreviewed by Neil Scolding, Bristol, UK.This article is made freely available for use in accordance withBMJ's website terms and conditions for the duration of theCOVID-19 pandemic or until otherwise determined by BMJ. Youmay use, download and print the article for any lawful, non-commercial purpose (including text and data mining) providedthat all copyright notices and trade marks are retained.

ORCID iDsSaúl Reyes http://orcid.org/0000-0002-3230-3263Monica Marta http://orcid.org/0000-0002-5464-9070Benjamin Turner http://orcid.org/0000-0002-7537-2357Ruth Dobson http://orcid.org/0000-0002-2993-585XKlaus Schmierer http://orcid.org/0000-0002-9293-8893G Giovannoni http://orcid.org/0000-0001-9995-1700

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Key points

► Unvaccinated individuals are at risk and create a riskof infection to the whole community.

► The evidence shows no link between vaccination anddevelopment of multiple sclerosis (MS), and noassociation at a population level between vaccinationand MS relapses.

► Poor vaccine uptake represents a serious threat topeople with MS and other patient groups who areimmunocompromised.

► People with MS may experience delays in startingdisease-modifying therapies if they need to bevaccinated.

► Although having MS does not automatically makevaccination high risk, disease-modifying therapiesmay influence the immune response againstimmunisations and their safety.

► Reviewing and updating immunisations should be anintegral part of routine MS care.

► Patient education is required proactively on the partof the primary, secondary and tertiary healthcareprofessionals to present correct information and topromote opportunities for people with MS to bevaccinated.

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