New pneumococcal conjugate vaccines for older and high-risk adults

British Columbia introduced the pneumococcal polysaccharide 23-valent (PPV23) vaccine in 1996 for bone marrow transplant recipients and asplenics. Over the next 2 years, the program expanded to residents of long-term care and adults 65 years and older, implemented in the year one turns 65. Select underlying medical conditions were added in later years, including people who are homeless, underhoused, or using illicit drugs, following a 2008 outbreak of serotype 5 disease.[1] A once-only second dose 5 years later is publicly funded for select groups but is not routinely provided in BC to older adults. Current indications are available on the PPV23 product page in the BC Immunization Manual.[2]

The PPV23 vaccine was designed to cover the majority of serotypes causing disease in adults. A recent systematic review and meta-analysis found no randomized trials of PPV23 efficacy but assessed results from nine observational studies of adults aged 60 years and older immunized within the prior 5 years and concluded that PPV23 vaccine effectiveness against vaccine-type invasive pneumococcal disease ranged from 42% to 64%, with slightly higher estimates for adults without immunocompromise; effectiveness against vaccine-type pneumonia has been variable, with some studies showing no effectiveness.[3]

Polysaccharides are T-cell-independent antigens and generally do not produce long-term B-cell memory or prime the immune system for subsequent response upon re-exposure (boosting). These vaccines are poorly immunogenic in infants, who experience the highest rates of invasive pneumococcal disease. As a result, conjugation technology to bind the polysaccharide to a protein carrier such as diphtheria toxoid was developed and results in a T-cell-dependent response with induction of B-cell memory.[4] Pneumococcal conjugate vaccines (PCVs) have been highly effective in young children, and their valencies have been designed around serotypes that cause disease in that age group. These vaccines have been used in the routine childhood immunization schedule since 2003, with initial introduction of a 7-valent vaccine (PCV7), replaced by a 13-valent vaccine (PCV13) in 2010. However, PCV13 had not been recommended for routine use in older adults by the Canadian National Advisory Committee on Immunization (NACI). This was despite favorable results in an efficacy trial of PCV13 published in 2015, conducted in the Netherlands, where polysaccharide vaccine had not been used in adults. The trial, Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), found 75% efficacy against invasive pneumococcal disease due to PCV13 serotypes and 45% efficacy against noninvasive PCV13-type pneumonia among adults aged 65 years and older.[5] Routine use of PCV13 in older adults was recommended in 2014 by the US Advisory Committee for Immunization Practices on the heels of a ninefold reduction in PCV13-type invasive pneumococcal disease in those aged 65 and older between 2000 and 2014, following the introduction of PCV vaccines for children, attributed to indirect protection due to reduced nasopharyngeal carriage among immunized children.[6] Continued declines in older adult disease were expected with the addition of direct protection from PCV13, in addition to PPV23, but were not observed despite moderate uptake of both vaccines in the older adult population. As a result, the US recommendation for PCV13 use in older adults was modified to shared decision making.

Two new PCVs have been authorized for use in adults in Canada: a 20-valent product (Prevnar20, Pfizer Canada ULC) and a 15-valent product (Vaxneuvance, Merck Canada Inc.). Approval was based on serological response, with comparisons to PCV13 and/or PPV23 serotypes. The immune response to some of the serotypes shared with PCV13 are lower, but the clinical relevance of this is unknown. Neither vaccine generates stronger response to serotype 3, the type most commonly associated with vaccine failure. Data on effectiveness will need to be generated in postmarketing use. NACI has recommended the use of PCV20 for older and high-risk adults to replace the use of PPV23. NACI has further recommended that if PCV15 is used in these adult populations, PPV23 should continue to be offered because of the benefit of protection from the additional strains.[7] Provincial and territorial public health programs will consider the introduction of these vaccines for older and high-risk adults in the coming months. In the meantime, these vaccines are commercially available for purchase in the private market.
—Monika Naus, MD, MHSc, FRCPC, FACPM
Medical Director, Immunization Programs and Vaccine Preventable Diseases Service, BC Centre for Disease Control

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This article is the opinion of the BC Centre for Disease Control and has not been peer reviewed by the BCMJ Editorial Board.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

References

1.    BC Centre for Disease Control. History of immunization in BC. In: Communicable disease control manual, chapter 2: Immunization (BC immunization manual). Accessed 30 Oct­ober 2023. www.bccdc.ca/health-professionals/clinical-resources/communicable-disease-control-manual/immunization.

2.    BC Centre for Disease Control. Part 4: Biological products (vaccines and immune globulins). In: Communicable disease control manual, chapter 2: Immunization (BC immunization manual). Accessed 30 October 2023. www.bccdc.ca/health-professionals/clinical-resources/communicable-disease-control-manual/immunization/biological-products.

3.    Farrar JL, Childs L, Ouattara M, et al. Systematic review and meta-analysis of the efficacy and effectiveness of pneumococcal vaccines in adults. Pathogens 2023;12:732.

4.    Pollard AJ, Perrett KP, Beverley PC. Maintaining protection against invasive bacteria with protein-polysaccharide conjugate vaccines. Nat Rev Immunol 2009;9:213-220.

5.    Bonten MJ, Huijts SM, Bolkenbaas M, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015;372:1114-1125.

6.    Matanock A, Lee G, Gierke R, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥ 65 years: Updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2019;68:1069-1075. Erratum in: MMWR Morb Mortal Wkly Rep 2020;68:1195.

7.    National Advisory Committee on Immunization. Recommendations on the use of conjugate pneumococcal vaccine – 15 valent (PNEU-C-15) and 20 valent (PNEU-C-20) in adults: Economic evidence supplementary appendix: An advisory committee statement. Public Health Agency of Canada, 24 February 2023. Accessed 30 October 2023. www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/public-health-level-recommendations-use-pneumococcal-vaccines-adults-including-use-15-valent-20-valent-conjugate-vaccines/economic-evidence-supplementary-appendix.html.