Why Doesn’t the CDC Recommend PCV13 Plus PCV21?

Hello, and thank you for your additional question on vaccines.

You are absolutely correct that when the vaccines are compared strictly by counting unique serotypes, receiving PCV13 followed by PCV21 would provide broader numerical coverage of serotypes than receiving PCV20 or PCV21 alone.

PCV13 and PCV21 share only four serotypes (3, 6A, 7F, and 19A), so the two together would cover 30 distinct serotypes compared with 20 or 21 from a single vaccine.

The missing piece is that pneumococcal vaccine recommendations aren't based only on how many different serotypes can theoretically be covered. They are more so based on which serotypes are currently causing the greatest amount of serious disease in the population being vaccinated.

Who Is Recommended to Receive a Pneumococcal Conjugate Vaccine

Before getting into serotype counts, it helps to know who these recommendations apply to.

In October 2024, the CDC's Advisory Committee on Immunization Practices lowered the age-based recommendation from 65 years to 50 years. Current CDC guidance recommends a single dose of a pneumococcal conjugate vaccine for:

• All adults aged 50 years and older who have not previously received a pneumococcal conjugate vaccine, or whose vaccination history is unknown
• Adults aged 19 through 49 years with certain underlying conditions or risk factors, such as diabetes, chronic heart, lung, liver, or kidney disease, cigarette smoking, alcohol use disorder, immunocompromising conditions, a cochlear implant, or a cerebrospinal fluid leak

PCV21 Was Designed Specifically Around Adult Disease

PCV21 is different from earlier pneumococcal conjugate vaccines because it was designed specifically around the serotypes now causing disease in adults. The CDC explains it this way:

"Unlike previous PCVs that were developed to target disease in children, PCV21 was developed to target pneumococcal disease in adults."

This is why PCV21 leaves out several serotypes included in PCV13, PCV15, and PCV20 (serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, and 23F, plus serotype 15B in PCV20) while adding eight serotypes that weren't included in any of those earlier vaccines.

Some of the omitted serotypes were originally important targets for childhood vaccination but now account for a relatively smaller share of adult invasive pneumococcal disease in much of the United States.

Routine childhood pneumococcal vaccination has also reduced the circulation of many of those older serotypes. This indirectly protects adults because children are less likely to carry and transmit them.

In contrast, the serotypes selected for PCV21 currently account for a very large proportion of serious pneumococcal infections in adults:

"During 2018–2022, pneumococcal serotypes contained in PCV21 caused approximately 80% of IPD cases among adults with indications for vaccination."

Broken out by group, the CDC's surveillance data for that period showed PCV21 serotypes accounted for roughly 84% of invasive pneumococcal disease in adults aged 65 and older, and roughly 81% in adults aged 19 through 64 with risk-based vaccine indications. The comparable figures for PCV20 were about 54% and 58%.

Why Not Routinely Give PCV13 and PCV21 Together?

There is a practical answer and a scientific one.

The practical answer is that PCV13 is no longer part of the adult pneumococcal vaccination schedule in the United States. It hasn't been routinely recommended for adults since the newer conjugate vaccines arrived, and Prevnar 13 was discontinued for the U.S. adult market in 2024.

It remains FDA-approved and may still be found in some clinics, and CDC guidance permits its use in the narrow situation where PCV15, PCV20, and PCV21 are all unavailable and the alternative would be leaving a patient unvaccinated. But it isn't a vaccine a clinician would ordinarily be able to start an adult series with today.

The scientific answer is that your proposed strategy would certainly cover more unique serotypes on paper, but there isn't evidence showing that intentionally giving both vaccines to every previously unvaccinated adult produces meaningfully better clinical protection than using one of the currently recommended strategies.

This point deserves emphasis, because it cuts in both directions.

ACIP's own review noted that no studies have assessed the efficacy or effectiveness of PCV21 against clinical outcomes such as invasive disease, pneumonia, or death. Licensure and the recommendation rest on immunogenicity data, meaning antibody responses measured in the laboratory, combined with surveillance data on which serotypes are circulating.

When outcome data are that limited, adding a second vaccine on the theory that more serotypes must mean more protection is a genuinely speculative move rather than a conservative one. The additional serotypes also aren't all equally likely to cause disease.

Giving two conjugate vaccines would also mean another injection, additional cost, and another opportunity for short-term adverse effects without a clearly established additional benefit.

All in all, vaccine recommendations generally try to balance serotype coverage, current disease patterns, safety, cost-effectiveness, and the simplicity of completing the vaccination series.

Final Words

Your observation about the limited overlap between PCV13 and PCV21 is correct, and the combination would cover more unique serotypes based on the serotypes in these vaccines. The reason it isn't a recommended starting strategy comes down to two things: PCV13 is no longer an available adult option in the United States, and the number of serotypes covered isn't the measure that drives these recommendations.

What matters more is how frequently those serotypes are currently causing disease, and whether adding another vaccine has been shown to provide meaningful additional protection.

Thanks again for reaching out.