What’s new in vaccines?

Since the start of the COVID-19 pandemic, there has been a lot of coverage of new vaccines, and for good reason. While the pandemic resulted in the unprecedented rapid development and mass administration of vaccines against COVID-19, an additional 12 new vaccine products were approved for use in Canada for diseases other than COVID-19 or influenza since 2020,1 including four for diseases that were not previously vaccine-preventable. This steady pace of new approvals is likely to persist, with 988 candidate vaccines in the global research and development pipeline (from preclinical through phase 3 trials) as of January 2023,2 including products targeting HIV infection, malaria and dengue.Given this rapid pace of growth, it can be challenging to keep current. As pharmacists are a trusted and common point of contact for people specifically seeking vaccines or with indications for vaccination, this article offers an overview of vaccines recently approved and/or marketed in Canada to help make sense of all these recent changes.New vaccines approved and/or marketed since 2020, by indication ChikungunyaChikungunya is a mosquito-borne virus endemic in tropical and subtropical regions worldwide. More than 100 countries have been affected within the last five years, including the Caribbean countries of Barbados, Jamaica and Saint Lucia, as well as Mexico and countries in Central America.3 In June 2024, Health Canada approved the first vaccine against chikungunya, Ixchiq, a live attenuated vaccine indicated for use in those age ≥ 18 years. It is administered as a single intramuscular (IM) dose.4Phase 3 trial safety and immunogenicity data (with measures of seroprotection based on earlier studies where sera from vaccinated humans was transferred to nonhuman primates that were then challenged with chikungunya virus) found seroprotection was induced in 98.9% (95% confidence interval [CI] 96.7%–99.8%) of vaccine recipients 28 days post-vaccination, persisting among 96.3% of recipients through day 180.5 Adverse effects occurring with > 10% frequency included headache (32.0% for vaccine vs. 15.5% for placebo), fatigue (28.7% vs. 13.3%), myalgia (24.3% vs. 7.9%), arthralgia (18.0% vs. 6.1%), injection site pain (13.4% vs. 9.8%), fever (13.9% vs. 1.3%) and nausea (11.3% vs. 6.1%). No differences related to immunogenicity or safety were observed between the 18–64 years of age and ≥ 65 years subgroups.5CholeraVaxchora is approved for the prevention of diarrheal disease caused by Vibrio cholerae serogroup O1 in people two to 64 years of age.6 It is a single-dose, live attenuated oral vaccine that is reconstituted by the patient prior to administration. Vaxchora should be taken at least 10 days prior to potential exposure. To protect the vaccine from the acidic environment of the stomach, it is consumed after adding the active component to a solution containing a buffer. The vaccine should be taken at least one hour before or one hour after any food or drink to avoid any interference with the protective effect of the buffer.6A phase 3 trial among healthy adults randomized to vaccine or placebo, and to challenge with live V. cholerae at 10 days or three months or no challenge, found vaccine efficacy against moderate to severe diarrhea to be 90.3% (95%CI 62.7%–100%) for those challenged at 10 days and 79.5% (95%CI 49.9%–100%) for those challenged at three months.7 The duration of protection is unknown, and the need for or timing of revaccination or booster doses has not yet been established.6 Adverse reactions occurring more frequently in vaccine vs. placebo recipients in adults were headache (28.9% vs. 23.6%) and diarrhea (3.6% vs. 1.6%), and in children included tiredness (35.7% vs. 30.7%), abdominal pain (27.8% vs. 18.7%) and lack of appetite (21.4% vs. 14.7%).6Vaxchora is the second vaccine marketed in Canada against cholera, alongside Dukoral. Both are oral vaccines with similar reconstitution processes, and both are indicated for ages two years or older. Key differences between Dukoral vs. Vaxchora include an additional indication for protection against heat-labile toxin producing enterotoxigenic Escherichia coli (LT-ETEC) for Dukoral, and regimens of two or three doses for Dukoral depending on age and reason for use versus a single dose for Vaxchora.8 The duration of protection of Dukoral against cholera is six months for children two to six years of age and two years for people six years or older, and when used to prevent LT-ETEC diarrhea it is three months across all ages.8The Committee to Advise on Tropical Medicine and Travel (CATMAT) has not yet released a comparative recommendation for use of these vaccines in Canadian travellers.EbolaErvebo is the only vaccine available (on a restricted basis) in Canada for protection against Ebola virus disease for adults ≥ 18 years of age; it is administered as a single IM dose.9,10 As it is a live vaccine, to reduce potential spread of Ebola, patients are advised to ensure the injection site or any subsequent vesicles (occurring among 1.5% of vaccine recipients) are covered with a bandage until there is no visible fluid leakage. They should also avoid close contact with high-risk individuals for at least six weeks following vaccination, including those who are immunocompromised, pregnant or breastfeeding, or less than one year of age.9Studies of Ervebo have only been performed in the context of outbreaks and post-exposure prophylaxis of healthcare and laboratory workers,10 but have demonstrated nearly 100% (95%CI 63.5%–100%) efficacy over 10–31 days. However, the duration of protection is not known.9 Adverse reactions to Ervebo are similar to other injectable vaccines, including injection site pain, swelling or redness, fever or chills, headache, fatigue, and myalgia or arthralgia.9Despite being a live vaccine indicated in adults, given the severity of Ebola, the Canadian Immunization Guide states it may be considered for use in children, during pregnancy, or in those who are immunocompromised following exposure to the virus and should ideally be given within 72 hours, but can be given up to 10 days post-exposure.10Access in Canada is currently restricted to the National Emergency Strategic Stockpile11 for management of exposures and potential outbreaks. It is not available for routine use or for use among travellers.Hepatitis BPreHevbrio is a recombinant hepatitis B vaccine indicated for adults ≥ 18 years of age, given as a series of three IM doses at 0, 1 and 6 months.12 It contains three antigens found on the surface of the hepatitis B virus (S, pre-S1, pre-S2) compared with other hepatitis B vaccines (Engerix-B, Recombivax HB, Twinrix) that contain only S protein; pre-S1 and pre-S2 are known to be more immunogenic than S.13 Another difference is that PreHevbrio is manufactured in mammalian cells (Chinese hamster ovary) rather than yeast, which is expected to result in recombinant proteins more similar in conformation to the virus that infects humans.14 This means that antibodies developed against the proteins in the vaccine can be expected to better align with proteins encountered through natural infection.Phase 3 randomized controlled trials of PreHevbrio vs. Engerix-B evaluated noninferiority in seroprotection rates in adults age ≥ 18 years and superiority in adults ≥ 45 years. Both endpoints were met, with a difference of 14.9% (95%CI 11.2%–18.6%) favouring PreHevbrio in those ≥ 18 years and 16.4% (95%CI 12.2%–20.7%) in those ≥ 45 years.12,15 Adverse effects from PreHevbrio are similar to other hepatitis B vaccines and include injection site pain, tenderness, itching, myalgia, fatigue and headache.12,15The National Advisory Committee on Immunization (NACI) has not yet deliberated on the use of PreHevbrio in Canada, and interchangeability of PreHevbrio with monovalent hepatitis B vaccines has not been determined.Meningococcal diseaseMenQuadfi is a conjugate vaccine indicated for protection against meningococcal disease (groups A, C, Y, W) among people ≥ 12 months of age. It is administered as a single IM dose.16 Adolescents and adults at continued risk of meningococcal disease who were vaccinated with a different quadrivalent meningococcal vaccine can receive a single dose of MenQuadfi as a booster if four or more years have elapsed since the previous vaccine.16 No data are available on the need for or timing of booster doses among people who have received MenQuadfi.Noninferiority of MenQuadfi has been demonstrated versus the three other available quadrivalent conjugate meningococcal vaccines across all four serogroups (see Table 1 for age groups and comparator vaccines studied).16 Pharmacists must be aware of different age indications across the various products: Menactra (9 months–55 years),17 MenQuadfi (≥ 12 months),16 Menveo (2 months–55 years),18 and Nimenrix (6 weeks–55 years).19 Adverse reactions with MenQuadfi across all ages include injection site pain, redness or swelling, as well as myalgia, malaise, headache and fever. Children under two years of age have also experienced vomiting, drowsiness, irritability and lost appetite.16NACI has not yet deliberated on the use of MenQuadfi,20 and the anticipated timing of its marketing in Canada is currently uncertain.Pneumococcal diseaseThree conjugate vaccines against pneumococcal disease have been recently approved, with two currently indicated for patients age six weeks of age or older (Prevnar 20 [20-valent] and Vaxneuvance [15-valent]) and one indicated for adults 18 years of age and older (Capvaxive [21-valent]).21,22 Other pneumococcal vaccines marketed in Canada include Pneumovax 23 (23-valent polysaccharide, indicated for age ≥ 2 years),23 Prevnar 13 (13-valent conjugate, age ≥ 6 weeks),24 and Synflorix (10-valent conjugate, age 6 weeks–5 years).25Currently, no efficacy or effectiveness data are available for either Prevnar 20 or Vaxneuvance;26 however, NACI concluded that Prevnar 20 and Vaxneuvance offer sufficient immune responses compared to other conjugate vaccines for shared serotypes among both children and adults. These vaccines also have the added benefits of providing protection against additional serotypes, and superior responses to Pneumovax 23 for shared serotypes in immunocompetent adults ≥ 65 years of age.21,27 No differences in safety or tolerability were noted across vaccines.Capvaxive contains eight serotypes not included in other pneumococcal vaccines (15A, 15C, 16F, 23A, 23B, 24F, 31 and 35B) and has demonstrated cross-protection against 6A and 15C, ultimately receiving approval to protect against 23 serotypes.22 Phase 3 trials in pneumococcal vaccine-naïve adults demonstrated noninferior immunogenicity versus Prevnar 20 for the 10 serotypes common to both vaccines, and superiority for all but one of the 11 serotypes not contained in Prevnar 20.28 A trial conducted among adults aged ≥ 50 years who had received Pneumovax 23, Prevnar 13 and/or Vaxneuvance at least one year prior to study enrollment found that Capvaxive was immunogenic regardless of previous vaccine(s) received.29 Comparable immunogenicity among serotypes shared with Vaxneuvance and Pneumovax 23 was observed. Similar tolerability and safety profiles were also observed across vaccines in both studies.Given the above immunogenicity and safety data, and knowledge that conjugate vaccines offer benefits over polysaccharide vaccines including a more robust and longer-lasting immune response and effectiveness in children < 2 years of age,30 NACI recommends the use of Prevnar 20 and Vaxneuvance at the public health level over other vaccines (see Table 2).27 NACI has not yet deliberated on the use of Capvaxive.Respiratory Syncytial Virus (RSV)Three vaccines for the prevention of lower respiratory tract disease caused by RSV are now approved in Canada:Abrysvo:31 Recombinant, single-dose IM vaccine without an adjuvant. Indicated for adults age ≥ 60 years and for use between 32–36 weeks of pregnancy to protect the infant during their first six months of life.Arexvy:32 Recombinant, single-dose IM vaccine containing the AS01E adjuvant. Indicated for adults age ≥ 60 years and for adults 50–59 years who are at increased risk for RSV disease. In a phase III clinical trial, increased risk was defined as having pre-existing and stable disease including chronic pulmonary disease (e.g., COPD, asthma and others), chronic cardiovascular disease (e.g., chronic heart failure, coronary artery disease, cardiac arrhythmia), diabetes, chronic kidney disease or chronic liver disease.mRESVIA:33 mRNA-based, single-dose IM vaccine. Indicated for adults age ≥ 60 years.When interpreting vaccine efficacy data, pharmacists should be aware of differing clinical definitions of RSV-associated lower respiratory tract infections across studies, making direct comparison of results and vaccines potentially problematic. With this in mind, Arexvy trials in adults age ≥ 60 years found vaccine efficacy of 82.6% and 94.1% against RSV infection and severe infection, respectively, after one RSV season, and 74.5% and 82.7%, respectively, after two RSV seasons.34 Noninferiority of the immune response (RSV-A and RSV-B neutralization titres) was demonstrated between adults age 50–59 with or without increased risk when compared against titres observed among a cohort age ≥ 60 years.35 In older adults, Abrysvo clinical trials reported vaccine efficacy of 65.1% and 88.9% against RSV infection with two or more or three or more signs/symptoms, respectively, after one RSV season, and 55.7% and 77.8%, respectively, after two RSV seasons.36 mRESVIA’s phase III clinical trial reported vaccine efficacy of 83.7% and 82.4% against RSV infection with two or more or three or more signs/symptoms, respectively, after a median 3.7 months of follow-up, and 63.3% and 63.0%, respectively, after a median 8.6 months of follow-up.33 This research is ongoing with a planned follow-up of 24 months.When given in pregnancy, Abrysvo was found to protect infants against medically attended severe lower respiratory tract RSV illness with vaccine efficacy of 81.8% at three months and 69.4% at six months.37Adverse effects are generally similar across vaccines; however, rates of local injection site pain are higher among recipients of Arexvy than Abrysvo and mRESVIA (60.9% vs. 40.6% and 55.9%, respectively),31-33 which may be attributable to the adjuvant component in Arexvy.Smallpox, mpoxACAM2000, authorized in December 2023, is a live vaccinia virus vaccine approved for use among those ≥ 16 years of age at high risk for smallpox infection.38 It should only be administered following training on administration of the vaccine by percutaneous scarification (uses a multiple-puncture technique with a bifurcated needle).39 Serious warnings exist related to myocarditis and/or pericarditis (5.7 cases per 1,000 recipients), as well as neurologic (e.g., encephalitis, encephalomyelitis), dermatologic (severe vaccinia skin infection; erythema multiforme major, including Stevens-Johnson syndrome) and ocular (keratitis, corneal scarring) complications.38 Given the eradication of naturally occurring smallpox worldwide and risks of morbidity and mortality from vaccination, access to ACAM2000 is restricted by the Public Health Agency of Canada.In addition, Imvamune (live attenuated, nonreplicating smallpox vaccine), which was initially authorized in 2013 for emergency use by the government, was subsequently approved in November 2020 for immunization against smallpox, mpox and related orthopoxviruses in those ≥ 18 years of age and at high risk for exposure.40 NACI recommends that individuals at high risk of mpox receive two doses of Imvamune as pre- or post-exposure prophylaxis as part of a routine immunization program.41A note on pandemic influenza vaccinesConsidering recent surveillance of H5N1 influenza cases,42 pandemic influenza vaccines will be briefly discussed. The Canadian Pandemic Influenza Preparedness Plan43 includes establishing contracts with some manufacturers to ensure access to vaccines that will be made available during an officially declared pandemic. Two IM vaccines have been approved in Canada for this purpose, both indicated for individuals ≥ 6 months of age:Foclivia, an H5N1 pandemic influenza vaccine adjuvanted with MF59,44 the same adjuvant as in the Fluad influenza vaccine.45Panenza, an H1N1 pandemic influenza vaccine not containing an adjuvant.46Both are given as a series of two doses at least 21 days apart, with a lower dose of Panenza used for those under three years of age. Strains to be used in both vaccines will be updated based on recommendations from the World Health Organization (WHO) upon declaration of a pandemic.How to keep currentPharmacists have adopted a key position as vaccinators in the community, with increasing involvement in care related to both routine immunization programs and privately purchased vaccines; however, staying current on changes in vaccine product availability and use is challenging. To support this, pharmacists can subscribe to two resources for updates by email:New or changed NACI statements and the Canadian Immunization GuidePharmacy Practice + Business e-newsletterSummaryTwelve new vaccine products have been recently approved for use in Canada for diseases other than COVID-19 or influenza. These include diseases with existing vaccines (cholera, hepatitis B, meningococcal disease, pneumococcal disease, smallpox) and newly vaccine-preventable diseases (chikungunya, Ebola, RSV), as well as two pandemic influenza vaccines as summarized in Table 3.Sherilyn Houle (sherilyn.houle@uwaterloo.ca) is an Associate Professor, University of Waterloo School of Pharmacy, in Waterloo, ON. Dr. Houle has practice experience in an international travel and immunizations clinic and research and teaching interests in pharmacy practice related to immunizations and travel medicine. She is the chair-elect of the Pharmacist Professional Group of the International Society of Travel Medicine and a member of the Ontario Immunization Advisory Committee.

What’s new in vaccines?

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