Pneumococcal polysaccharide serotype 23A conjugated to CRM197

Table of contents

• What is pneumococcal polysaccharide serotype 23A?
• How does pneumococcal polysaccharide serotype 23A work?
• Which conditions is it used or studied for?
• How is pneumococcal polysaccharide serotype 23A given?
• What do the clinical trials show?
• Who can take part in these trials?
• What are the trials measuring?
• What side effects are known?

What is pneumococcal polysaccharide serotype 23A?

Pneumococcal polysaccharide serotype 23A conjugated to CRM197 is a bacterial polysaccharide from the capsule of Streptococcus pneumoniae (pneumococcus) that is chemically linked to a carrier protein called CRM197. It is not used on its own; it is one of 21 pneumococcal polysaccharide serotypes included in CAPVAXIVE, a pneumococcal polysaccharide conjugate vaccine (21-valent).^[1] The full registry name lists 21 serotypes conjugated to CRM197, including serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F and 35B.^[1]

The vaccine is authorised as a medicine in the European Union, with authorisation record EU/1/25/1913/001, and the authorisation holder is Merck Sharp & Dohme B.V.^[1] The product name is CAPVAXIVE solution for injection in pre-filled syringe, pneumococcal polysaccharide conjugate vaccine (21-valent).^[1] The substance is part of a fixed combination product in one product record.^[1]

How does pneumococcal polysaccharide serotype 23A work?

Pneumococcal conjugate vaccines work by presenting bacterial polysaccharides from the pneumococcal capsule to the immune system. The polysaccharides are conjugated to a carrier protein, CRM197, which helps the immune system recognise them and produce a stronger, longer-lasting antibody response. In the supplementary sources, the 20-valent pneumococcal conjugate vaccine is described as containing pneumococcal polysaccharide serotypes conjugated to CRM197 carrier protein, approximately 51 µg per dose, adsorbed on aluminium phosphate.^[3] The same conjugation approach is described for the 20-valent vaccine in the MHRA paediatric investigation plan, where each serotype is conjugated to CRM197 carrier protein and adsorbed on aluminium phosphate.^[4] The 21-valent vaccine CAPVAXIVE follows the same principle, with serotype 23A included among its 21 serotypes.^[1]

Which conditions is it used or studied for?

The vaccine containing pneumococcal polysaccharide serotype 23A is studied in the following conditions:

• Asplenia — a condition in which a person has no spleen or the spleen does not function. People without a spleen are at higher risk of pneumococcal infections.^[1]
• Medium or high risk for pneumococcal invasive infection — adults who are at increased risk of serious pneumococcal disease, including those with an acute febrile illness at the time of vaccination.^[2]

The therapeutic area of the registry records covers bacterial infections and mycoses, immune system processes and immune system diseases.^[1] The supplementary source describes the 20-valent pneumococcal conjugate vaccine as intended to protect against invasive pneumococcal disease in adults aged 65 years and above.^[3]

How is pneumococcal polysaccharide serotype 23A given?

The vaccine is given as a solution for injection in a pre-filled syringe, by intramuscular injection. The dose is 0.5 ml.^[1] In the two registered trials, CAPVAXIVE is administered as a single intramuscular injection of 0.5 ml.^[1][2] The comparator vaccine, Prevenar 20, is also given as a 0.5 ml intramuscular injection.^[1][2]

What do the clinical trials show?

Two Phase 3 interventional trials are registered for the vaccine containing pneumococcal polysaccharide serotype 23A. Both are authorised, meaning they have received regulatory approval to proceed, and both compare CAPVAXIVE with Prevenar 20, a 20-valent pneumococcal conjugate vaccine.^[1][2] The first trial (2024-515363-63-00) studies 70 participants with asplenia, examining the response to a booster vaccination with CAPVAXIVE at least 12 months after primary vaccination with Prevenar 20.^[1] The second trial (NCT06822907) studies 1,160 participants at medium or high risk for pneumococcal invasive infection, comparing vaccination during an acute febrile illness with vaccination after the illness has resolved.^[2]

Who can take part in these trials?

The trials enrol different patient groups. The asplenia trial includes patients without a spleen, vaccinated either before or after spleen removal.^[1] The larger trial includes unvaccinated patients at medium or high risk for pneumococcal infections who have an acute febrile illness at the time of enrolment.^[2] The supplementary source describes a separate observational study of the 20-valent vaccine in adults aged 65 years and above, but that study is not part of the two registered trials for the 21-valent vaccine.^[3]

What are the trials measuring?

Both trials measure the immune response to vaccination. The asplenia trial measures the mean fold change of pneumococcal serotype-specific IgG antibody concentrations against serotypes common to both vaccines, 2–3 weeks after booster vaccination with CAPVAXIVE.^[1] The larger trial measures the proportion of immune "good responders" one month after vaccination, defined by seroconversion — a two-fold or four-fold increase in vaccine-type IgG antibodies — for at least 10 of 13 tested vaccine serotypes, together with an immune protective response defined as ELISA IgG of at least 1.3 µg/ml in at least 10 of 13 tested serotypes.^[2]

What side effects are known?

A study of adverse events following pneumococcal vaccines from the Korea Adverse Event Reporting System database, 2005–2016, examined signal detection for pneumococcal vaccines.^[5] The source provided does not list specific side effects for the 21-valent vaccine in the extracted content, so no specific side effect frequencies for CAPVAXIVE can be stated here.^[5]