Recommendations on the use of pneumococcal vaccines in adults, including pneu-c-21: Supplemental clinical evidence synthesis
Organization: Public Health Agency of Canada
Date published: 2024-11-15
Cat.: HP40-373/2024-2E-PDF
ISBN: 978-0-660-74240-3
Pub.: 240600
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Preamble
The National Advisory Committee on Immunization (NACI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with independent, ongoing and timely medical, scientific, and public health advice in response to questions from PHAC relating to immunization.
In addition to burden of disease and vaccine characteristics, PHAC has expanded the mandate of NACI to include the systematic consideration of programmatic factors in developing evidence based recommendations to facilitate timely decision-making for publicly funded vaccine programs at provincial and territorial levels.
The additional factors to be systematically considered by NACI include: economics, ethics, equity, feasibility, and acceptability. Not all NACI statements will require in-depth analyses of all programmatic factors. While systematic consideration of programmatic factors will be conducted using evidence-informed tools to identify distinct issues that could impact decision-making for recommendation development, only distinct issues identified as being specific to the vaccine or vaccine-preventable disease will be included.
This statement contains NACI's independent advice and recommendations, which are based upon the best current available scientific knowledge. This document is being disseminated for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph. Recommendations for use and other information set out herein may differ from that set out in the product monographs of the Canadian manufacturers of the vaccines. Manufacturer(s) have sought approval of the vaccines and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.
This document contains supplemental information for the NACI guidance on Recommendations on the use of pneumococcal vaccines in adults, including PNEU-C-21. A summary of the clinical trials is provided in Table 6 of NACI statement.
Measured outcome | Vaccine naïve adults | Previously vaccinated adults ≥50 years of age |
---|---|---|
Immunogenicity | ||
Opsonophagocytic activity (OPA) geometric mean titer (GMT) | OPA GMTs for the common serotypes shared between Pneu-C-21 and Pneu-P-23 were comparable. For the 9 unique serotypes to Pneu-C-21, OPA GMTs were higher in the Pneu-C-21 group compared to the Pneu-P-23 group. | Immune responses were overall comparable between intervention groups (Pneu-C-21 or Pneu-P-23) for common serotypes; OPA GMT point estimates following Pneu-C-21 administration were higher for some serotypes and lower for others. In adults previously immunized with Pneu-C-13, Pneu-P-23 or Pneu-C-13+Pneu-P-23, Pneu-C-21 was immunogenic for all 21 serotypes contained in the vaccine in all age groups (as assessed by serotype-specific OPA GMTs at 30 days postvaccination). |
% with ≥4-fold rise in OPA responses | The proportions of participants with a ≥4-fold rise in OPA responses were generally comparable in the intervention groups for the common serotypes. The proportion of participants with a ≥4-fold rise in OPA responses was higher in the Pneu-C-21 group for the serotypes unique to Pneu-C-21. | In adults previously immunized with Pneu-C-13, Pneu-P-23 or Pneu-C-13+Pneu-P-23, Pneu-C-21 was immunogenic for all 21 serotypes contained in the vaccine (as assessed by the proportions of participants with a ≥4-fold rise in serotype-specific OPA responses) |
Safety | ||
Vaccine-related serious adverse events (SAEs) | No vaccine-related SAEs were observed in either group. | No vaccine-related SAEs were observed in either group. |
Total SAEs | 18 to 49 years of age
≥50 years of age
|
Cohort 2; participants who previously received PCV13 >1 year prior to study enrollment:
|
Death | No vaccine-related deaths were observed. | No vaccine-related deaths were observed. |
Outcome | Number of studies, study design | Pneu-C-21 | Pneu-C-20 | Impact: quantitative or narrative | Certainty of evidence | Comments/summary |
---|---|---|---|---|---|---|
Day 1 through duration of participation in study | ||||||
Vaccine-related SAEs | 1 RCT (V116-003) | N=0/590 | N=0/590 | No vaccine-related SAEs were observed in either group. | ModerateFootnote a | There is probably little to no difference between vaccines in the occurrence of vaccine-related SAEs. |
Total SAEs | 1 RCT (V116-003) | N=11/590 | N=16/590 |
|
ModerateFootnote a | There is probably little to no difference between vaccines in the occurrence of SAEs. |
Death | 1 RCT (V116-003) | N=2/590 | N=2/590 |
|
ModerateFootnote a | There is probably little to no difference between vaccines in the occurrence of deaths. |
|
Outcome | Number of studies, study design | Pneu-C-21 | Pneu-C-20 | Impact: quantitative or narrative | Certainty of evidence | Comments/summary |
---|---|---|---|---|---|---|
Day 1 through duration of participation in study | ||||||
Vaccine-related SAEs | 1 RCT (V116-003) | No risk: N=0/730 | No risk: N=0/766 | No vaccine-related SAEs were observed in either group. | ModerateFootnote a | There is probably little to no difference between vaccines in the occurrence of vaccine-related SAEs. |
Single risk factor: N=0/347 | Single risk factor: N=0/328 | |||||
2 or more risk factors: N=0/100 | 2 or more risk factors: N=0/81 | |||||
Total SAEs | 1 RCT (V116-003) | No risk: N=10/730 | No risk: N=13/766 |
|
ModerateFootnote a | There is probably little to no difference between vaccines in the occurrence of SAEs. |
Single risk factor: N=3/347 | Single risk factor: N=8/328 |
|
||||
2 or more risk factors: N=6/100 | 2 or more risk factors: N=3/81 |
|
||||
Death | 1 RCT (V116-003) | No risk:N=2/730 | No risk: N=1/766 |
|
ModerateFootnote a |
|
Single risk factor: N=1/347 | Single risk factor: N=0/328 |
|
||||
2 or more risk factors: N=1/100 | 2 or more risk factors: N=1/81 |
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|
Outcome | Number of studies, study design | Pneu-C-21 | Pneu-C-20 | Impact: quantitative or narrative | Certainty of evidence | Comments/summary |
---|---|---|---|---|---|---|
Day 1 through duration of participation in study | ||||||
Vaccine-related SAEs | 1 RCT (V116-003 Cohort 2) | N=0/787 | N=0/685 | No vaccine-related SAEs were observed in either group. | ModerateFootnote a | There is probably little to no difference between vaccines in the occurrence of vaccine-related SAEs. |
Total SAEs | 1 RCT (V116-003 Cohort 2) | N=9/787 | N=11/685 |
|
ModerateFootnote a | There is probably little to no difference between vaccines in the occurrence of SAEs. |
Death | 1 RCT (V116-003 Cohort 2) | N=2/787 | N=0/685 |
|
ModerateFootnote a | No deaths determined to be related to study vaccine.There is probably little to no difference between vaccines in the occurrence of deaths. |
|
Outcome | Number of studies, study design | Pneu-C-21 | Pneu-P-23 | Impact: quantitative or narrative | Certainty of evidence | Comments/summary |
---|---|---|---|---|---|---|
Day 1 through duration of participation in study | ||||||
Vaccine-related SAEs | 3 RCTs (V116-001; Haranaka et al.; V116-004) | V116-001
|
V116-001
|
No vaccine-related SAEs were reported across studies. | Not assessed | Across all 3 studies comparing Pneu-C-21 to Pneu-P-23, safety and reactogenicity was comparable between the products. |
Haranaka et al. N=0/51 | Haranaka et al. N=0/51 | |||||
V116-004 N=0/1,616 | V116-004 N=0/541 | |||||
Total = 0/1,921 | Total = 0/846 | |||||
Total SAEs | 3 RCTs (V116-001; Haranaka et al.; V116-004) | V116-001
|
V116-001
|
Relative effects: Peto OR 0.84 (95% CI: 0.37 to 1.93)Absolute effects: 3 fewer per 1,000 (8 fewer to 8 more) | Not assessed | SAEs occurred infrequently across studies and with similar proportions across intervention groups. |
Haranaka et al. N=0/51 |
Haranaka et al. N=0/51 |
|||||
V116-004 N=14/1,616 |
V116-004 N=6/541 |
|||||
Total = 18/1,870 | Total = 9/795 | |||||
Death | 3 RCTs (V116-001; Haranaka et al.; V116-004) | V116-001
|
V116-001
|
No deaths were related to the study vaccine. | Not assessed | No vaccine-related deaths were reported across studies. |
Haranaka et al. N=0/51 |
Haranaka et al. N=0/51 |
|||||
V116-004 N=0/1,616 | V116-004 N=1/541 | |||||
Total = 1/1,921 | Total = 1/846 |
Outcome | Number of studies, study design | Pneu-C-21 | Pneu-P-23 | Impact: quantitative or narrative | Certainty of evidence | Comments/summary |
---|---|---|---|---|---|---|
Day 1 through duration of participation in study | ||||||
Vaccine-related SAEs | 1 RCT (V116-006 Cohort 2) | N=0/174 | N=0/85 | No vaccine-related SAEs were observed in either group. | Not assessed | In adults who received prior pneumococcal vaccines, Pneu-C-21 was well tolerated with a safety profile that was generally comparable to vaccination with Pneu-P-23. |
Total SAEs | 1 RCT (V116-006 Cohort 2) | N=2/174 | N=3/85 | The proportion of participants with SAEs was low (<4%) and generally comparable between intervention groups. | Not assessed | There is probably little to no difference between vaccines in the occurrence of SAEs. |
Death | 1 RCT (V116-006 Cohort 2) | N=0/174 | N=0/85 | No vaccine-related deaths were reported in any of the study groups. | Not assessed | There is probably little to no difference between vaccines in the occurrence of deaths. |
Outcome | Number of studies, study design | Pneu-C-21 | Pneu-C-15 + Pneu-P-23 | Impact: quantitative or narrative | Certainty of evidence | Comments/summary |
---|---|---|---|---|---|---|
Day 1 through duration of participation in study | ||||||
Vaccine-related SAEs | 1 RCT (V116-007) | N=0/155 | N=0/155 |
|
Not assessed | There is probably little to no difference between vaccines in the occurrence of vaccine-related SAEs. |
Total SAEs | 1 RCT (V116-007) | N=4/155 | N=6/155 | The proportions of participants with SAEs were low (<4%) and generally comparable in both intervention groups. |
Not assessed | There is probably little to no difference between vaccines in the occurrence of SAEs. |
Death | 1 RCT (V116-007) | N=1/155 | N=0/155 | One death was reported for a participant who received Pneu-C-21. No additional information was provided. | Not assessed | There is probably little to no difference between vaccines in the occurrence of deaths. |
Outcome | Number of studies, study design | Number of study participants | Impact: quantitative or narrative | Certainty of evidence | Comments/summary | |
---|---|---|---|---|---|---|
Pneu-C-21 | Pneu-C-20 | |||||
30 days post vaccination | ||||||
OPA GMT (common serotypes) | 1 RCT (V116-003) | Range N= 579-586 analysed across common serotypes | Range N= 575-585 analysed across common serotypes | Distribution of serotype-specific OPA titres was generally comparable between groups for common serotypes. This was also observed for age subgroups of individuals 65 to 74 years of age and individuals 75 years of age and older. | Moderate | There is probably little to no difference between vaccines in the distribution of serotype-specific OPA titres for common serotypes. |
OPA GMT (unique serotypes) | 1 RCT (V116-003) | Range N= 579-586 analysed across unique serotypes | Range N= 575- 585 analysed across unique serotypes | Serotype-specific OPA titres numerically higher for most Pneu-C-21 unique serotypes. This was also observed for age subgroups of individuals 65 to 74 years of age and individuals 75 years of age and older. | Moderate | The distribution of serotype-specific OPA titres for unique serotypes is generally higher for Pneu-C-21. |
≥4-fold rise in OPA responses for unique serotypes | 1 RCT (V116-003) | N= 590 analysed across unique serotypes | N= 590 analysed across unique serotypes | The proportion of seroresponders was numerically higher against all unique serotypes for Pneu-C-21 compared to Pneu-C-20. However, the difference in the proportion of responders between Pneu-C-21 and Pneu-C-20 was lowest for serotype 15C. The difference in the proportion of seroresponders to Pneu-C-21 and Pneu-C-20 was comparable between individuals 65-74 years of age and individuals 75 years of age and older. | Moderate | N/A |
Outcome | Number of studies, study design | Number of study participants | Impact: quantitative or narrative | Certainty of evidence | Comments/summary | |
---|---|---|---|---|---|---|
Pneu-C-21 | Pneu-C-20 | |||||
30 days post vaccination | ||||||
OPA GMT (common serotypes) | 1 RCT (V116-003) | Range N= 435-440 analysed across common serotypes | Range N= 397-404 analysed across common serotypes | Distribution of serotype-specific OPA titres was generally comparable between groups for common serotypes. | ModerateFootnote a | There is probably little to no difference between vaccines in the distribution of serotype-specific OPA titres for common serotypes. |
OPA GMT (unique serotypes) | 1 RCT (V116-003) | Range N= 411-441 analysed across unique serotypes | Range N= 385-404 analysed across unique serotypes | Serotype-specific OPA titres were significantly higher for nearly all Pneu-C-21 unique serotypes. | ModerateFootnote a | The distribution of serotype-specific OPA titres for unique serotypes is generally higher for Pneu-C-21. |
≥4-fold rise in OPA responses for unique serotypes | 1 RCT (V116-003) | N=447 analysed across unique serotypes | N=409 analysed across unique serotypes | Proportion of seroresponders was numerically higher against all unique serotypes for Pneu-C-21 compared to Pneu-C-20. | ModerateFootnote a | N/A |
|
Outcome | Number of studies, study design | Number of study participants | Impact: quantitative or narrative | Certainty of evidence | Comments/summary | |
---|---|---|---|---|---|---|
Pneu-C-21 | Pneu-C-20 | |||||
30 days post vaccination | ||||||
OPA GMT (common serotypes) | 1 RCT (V116-003 Cohort 2) | N=200 analysed across common serotypes | N=100 analysed across common serotypes | Distribution of serotype-specific OPA titres was generally comparable between groups for common serotypes. | ModerateFootnote a | There is probably little to no difference between vaccines in the distribution of serotype-specific OPA titres for common serotypes. |
OPA GMT (unique serotypes) | 1 RCT (V116-003 Cohort 2) | N=200 analysed across unique serotypes | N=100 analysed across unique serotypes | Serotype-specific OPA titres were significantly higher for Pneu-C-21 unique serotypes. | ModerateFootnote a | The distribution of serotype-specific OPA titres for unique serotypes is higher for Pneu-C-21. |
≥4-fold rise in OPA responses for unique serotypes (data not available for common serotypes) | 1 RCT (V116-003 Cohort 2) | N=200 analysed across unique serotypes | N=100 analysed across unique serotypes | The proportion of seroresponders was numerically higher against all unique serotypes for Pneu-C-21 compared to Pneu-C-20. | ModerateFootnote a | N/A |
|
Outcome | Number of studies, study design | Number of study participants | Impact: quantitative or narrative | Certainty of evidence | Comments/summary | |
---|---|---|---|---|---|---|
Pneu-C-21 | Pneu-P-23 | |||||
30 days post vaccination | ||||||
OPA GMT (common serotypes) | 3 RCTs (V116-001; Haranaka et al.; V116-004) | Haranaka et al.: 65 years of age and older: N=34 |
Haranaka et al.: 65 years of age and older: N=34 |
Across all 3 studies comparing Pneu-C-21 to Pneu-P-23, Pneu-C-21 was immunogenic for all 21 serotypes contained in the vaccine in all age groups (as assessed by serotype-specific OPA GMTs at 30 days postvaccination). OPA GMTs for the 12 common serotypes shared between Pneu-C-21 and Pneu-P-23 were comparable. |
Not assessed | There is probably little to no difference between vaccines in the distribution of serotype-specific OPA titres for common serotypes. |
V116-001: 18 to 49 years of age (2 cohorts, N=30 each): Range N=27 to 29 ≥50 years of age: N= 252 |
V116-001: 18 to 49 years of age: Range N=27 to 30 ≥50 years of age: N=254 |
|||||
V116-004 : Range N=1,573 to 1,593 analysed across serotypes (combined lots) | V116-004 : Range N= 530 to 537 analysed across serotypes | |||||
OPA GMT (unique serotypes) | 3 RCTs (V116-001; Haranaka et al.; V116-004) | Haranaka et al.: N=34 |
Haranaka et al.: N=34 |
For the 9 unique serotypes to Pneu-C-21, OPA GMTs were numerically higher in the Pneu-C-21 group compared to the Pneu-P-23 group. | Not assessed | The distribution of serotype-specific OPA titres for unique serotypes is generally higher for Pneu-C-21. |
V116-001: 18 to 49 years of age: Range N= 27 to 29 ≥50 years of age: N=252 |
V116-001: 18 to 49 years of age: Range N= 28 to 29 ≥50 years of age: N=254 |
|||||
V116-004: Range N= 1,520 to 1,583 (combined lots) | V116-004 : Range N= 512 to 537 | |||||
≥4-fold rise in OPA responses for unique serotypes | 3 RCTs (V116-001; Haranaka et al.; V116-004) | Haranaka et al.: Outcome not assessed |
Haranaka et al.: Outcome not assessed |
The proportions of participants with a ≥4-fold rise in OPA responses from pre-vaccination to 30 days postvaccination were higher in the Pneu-C-21 group for the serotypes unique to Pneu-C-21. | Not assessed | N/A |
V116-001: 18 to 49 years of age: Range N= 27 to 29 ≥50 years of age: N= 252 |
V116-001: 18 to 49 years of age: Range N= 28 to 30 ≥50 years of age: N= 254 |
|||||
V116-004: Range N=950 to 1,360 (combined lots) | V116-004: Range N= 334 to 465 | |||||
≥4-fold rise in OPA responses for common serotypes | 3 RCTs (V116-001; Haranaka et al.; V116-004) | Haranaka et al.: Outcome not assessed | Haranaka et al.: Outcome not assessed | The proportions of participants with a ≥4-fold rise in OPA responses from pre-vaccination to 30 days postvaccination were generally comparable in the Pneu-C-21 and Pneu-P-23 intervention groups for the common serotypes. | Not assessed | N/A |
V116-001: 18 to 49 years of age: Range N= 28 to 29 ≥50 years of age: N= 252 |
V116-001: 18 to 49 years of age: Range N= 27 to 30 ≥50 years of age: N= 254 |
|||||
V116-004: Range N=950 to 1,360 (combined lots) | V116-004: Range N= 334 to 465 |
Outcome | Number of studies, study design | Number of study participants | Impact: quantitative or narrative | Certainty of evidence | Comments/summary | |
---|---|---|---|---|---|---|
Pneu-C-21 | Pneu-P-23 | |||||
30 days post vaccination | ||||||
OPA GMT (common serotypes) | 1 RCT (V116-006 Cohort 2) | V116-006 Range: N=125-161 across common serotypes |
V116-006 Range: N=58-75 across common serotypes |
Immune responses were overall comparable between intervention groups (Pneu-C-21 or Pneu-P-23) for common serotypes; OPA GMT point estimates following Pneu-C-21 administration were higher for some serotypes and lower for others. | Not assessed | There is probably little to no difference between vaccines in the distribution of serotype-specific OPA titres for common serotypes. |
OPA GMT (unique serotypes) | 1 RCT (V116-006) | V116-006 Range: N=134-160 across unique serotypes |
V116-006 Range: N=60-76 across unique serotypes |
In adults previously immunized with Pneu-C-13, Pneu-P-23 or Pneu-C-13+Pneu-P-23, Pneu-C-21 was immunogenic for all 21 serotypes contained in the vaccine in all age groups (as assessed by serotype-specific OPA GMTs at 30 days postvaccination). | Not assessed | N/A |
≥4-fold rise in OPA responses for unique serotypes | 1 RCT (V116-006 Cohort 2) | V116-006 Range: N=110-157 across unique serotypes |
V116-006 Range: N=38-72 across unique serotypes |
In adults previously immunized with Pneu-C-13, Pneu-P-23 or Pneu-C-13+Pneu-P-23, Pneu-C-21 was immunogenic for all 21 serotypes contained in the vaccine (as assessed by the proportions of participants with a ≥4- fold rise in serotype-specific OPA responses). | Not assessed | N/A |
Outcome | Number of studies, study design | Number of study participants | Impact: quantitative or narrative | Certainty of evidence | Comments/summary | |
---|---|---|---|---|---|---|
Pneu-C-21 | Pneu-C-15 + Pneu-P-23 | |||||
30 days post vaccination | ||||||
OPA GMT (common serotypes) | 1 RCT (V116-007) | Range: N=123-137 across common serotypes | Range: N=123-130 across common serotypes | Pneu-C-21 elicited immune responses that were generally comparable to Pneu-C-15 + Pneu-P-23 for the common serotypes. | Not assessed | There is probably little to no difference between vaccines in the distribution of serotype-specific OPA titres for common serotypes. |
OPA GMT (unique serotypes) | 1 RCT (V116-007) | Range: N=127-137 across unique serotypes | Range: N=98-128 across unique serotypes | Pneu-C-21 elicited immune responses that was higher compared to Pneu-C-15 + Pneu-P-23 for the unique serotypes. | Not assessed | The distribution of serotype-specific OPA titres for unique serotypes is higher for Pneu-C-21. |
GRADE certainty of evidence rating | Description |
---|---|
High | Very confident that the true effect lies close to that of the effect estimate. |
Moderate | Moderately confident: the true effect is likely to be close to the effect estimate, but there is a possibility that it is substantially different. |
Low | Limited confidence in the effect estimate: the true effect may be substantially different from the effect estimate. |
Very low | Very little confidence in the effect estimate: true effect likely to be substantially different from the effect estimate. |
Abbreviations
- CI
- Confidence interval
- GMT
- Geometric mean titer
- NACI
- National Advisory Committee on Immunization
- OPA
- Opsonophagocytic activity
- OR
- Odds ratio
- Pneu-C-15
- 15-valent pneumococcal conjugate vaccine
- Pneu-C-20
- 20-valent pneumococcal conjugate vaccine
- Pneu-C-21
- 21-valent pneumococcal conjugate vaccine
- Pneu-P-23
- 23-valent pneumococcal polysaccharide vaccine
- PHAC
- Public Health Agency of Canada
- RR
- Relative risk
- SAE
- Serious adverse event
References
References:
- Footnote 1
-
Merck Canada Inc. Personal communication. Merck clinical dossier submission for V116 (Capvaxive), 21-valent pneumococcal conjugate vaccine. 2023 Dec 8.
- Footnote 2
-
Haranaka M, Yono M, Kishino H, et al. Safety, tolerability, and immunogenicity of a 21- valent pneumococcal conjugate vaccine, V116, in Japanese healthy adults: A Phase I study. Hum Vaccin Immunother. 2023 Aug 1;19(2):2228162. http://doi.org/10.1080/21645515.2023.2228162.
- Footnote 3
-
Merck Canada Inc. Personal communication. Request for data on V116-007 received 2024 Apr 24.
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