How effective is Pneumococcal vaccine?

The initial pre-licensing clinical trials of a pneumococcal capsular polysaccharide involved a comparison study of the effectiveness of a 6-valent polysaccharide vaccine against a 12-valent polysaccharide vaccine. The study involved South African gold miners between the ages of 16 and 58, a population noted to be at a higher risk for pneumococcal pneumonia. The 6-valent vaccine was reported to be 76 percent effective while the 12-valent vaccine was found to be 92 percent effective against the particular pneumococcal strains found in the vaccine.   

The long-term effectiveness of the vaccine was not measured as the study was limited to only one year. An additional polysaccharide vaccine effectiveness study involving both a 6-valent and 13-valent polysaccharide vaccine found a 79 percent reduction in pneumococcal pneumonia and an 82 percent reduction in pneumococcal bacteremia caused by the strains found in the vaccine. 

In the United States, two post-licensing trials on the effectiveness of the original 14-valent pneumococcal polysaccharide vaccine in the elderly or persons with chronic medical conditions found the vaccine to be ineffective against bronchitis and pneumonia.     

Additional research on the effectiveness of the pneumococcal polysaccharide vaccine based on the CDC’s pneumococcal surveillance system found the vaccine to be 57 percent effective against the serotypes found within PNEUMOVAX23 (PPSV23) in persons six years of age and older, between 65 and 84 percent effective in persons with chronic illness (e.g. diabetes, congestive heart failure, and COPD), and 75 percent effective in healthy persons 65 and older. Vaccine effectiveness, however, could not be determined in certain populations of individuals with immunosuppressive conditions. 

When PNEUMOVAX23 (PPSV23) was administered in combination with ZOSTAVAX, Merck’s live attenuated shingles vaccine, shingles antibody levels were found to be significantly lower when compared to administering the shingles vaccine four weeks after PNEUMOVAX23 administration. 

A 2008 study found that while PPSV23 reduced the risk of invasive pneumococcal disease in the elderly by 38 percent, it had no impact on pneumonia rates.  In 2010, researchers found the vaccine to be completely ineffective at reducing the rates of hospitalization or death in persons previously treated for community acquired pneumonia.  The vaccine was also found to be ineffective in both transplant patients,  and persons with HIV who had low CD4+ cell counts  and the vaccine did not reduce the rates of pneumonia in persons with rheumatoid arthritis. 

Information on pneumococcal conjugate vaccine efficacy found in the Prevnar 13(PCV13) product insert reports information pertaining to the original PCV vaccine, Prevnar (PCV7). PCV7 was reported to be 100 percent effective at preventing invasive disease caused by S. pneumoniae during the pre-licensing clinical trial which took place over a 34-month period. An eight-month extended follow-up of vaccine recipients reported the vaccine’s efficacy to be between 93 and 97.4 percent. 

In clinical studies pertaining to the PCV vaccine for the prevention of acute otitis media, studies found PCV7 to be only seven percent effective at preventing acute otitis media and children who received PCV7 were noted to be at a higher risk for developing acute otitis media from strains not covered by the vaccine. Studies also found that PCV7 reduced the need for tympanostomy tubes (ear tubes) by 20 percent. 

One large scale study involving nearly 85,000 adults 65 years of age and older found PCV13 to be 45.6 percent effective against vaccine-type pneumococcal pneumonia, 45 percent effective against vaccine-type non-bacteremic pneumococcal pneumonia and 75 percent effective against all vaccine-type invasive pneumococcal disease. 

The Prevnar 13 (PCV13) product insert also states that effectiveness of the vaccine cannot be established in the following population: 

• Infants born prematurely
• Persons with HIV-infection
• Children with sickle cell disease
• Persons who had received an allogeneic hematopoietic stem cell transplant

Following FDA approval of the first pneumococcal conjugate vaccine, Prevnar (PCV7), researchers discovered that while the vaccine was effective in reducing the risk of infection caused by the seven strains found within the vaccine, strains not found within the vaccine began to emerge and increase in prevalence. Most notably, strain 19A, a highly virulent strain resistant to all antibiotics FDA approved for use in children for the treatment of acute otitis media, emerged.   

In addition to pneumococcal strain replacement, the introduction of PCV7 resulted in a significant increase in pneumococcal empyema, a complication of pneumococcal pneumonia resulting in an accumulation of pus between the lungs and the inner aspect of the chest wall.    The most common strains causing empyema were found to be pneumococcal strains 1, 3 and 19A, three strains not covered in the PCV7 vaccine.   

While invasive disease from vaccine-type strains decreased significantly within the first four years following the introduction of PCV7, antibiotic resistant non-vaccine type strains began to take their place.  In one particular population of Alaska Native children, the introduction of the PCV7 vaccine caused a 140 percent increase of invasive pneumococcal disease from strains not found in the vaccine. 

Rates of pneumococcal meningitis by antibiotic resistant strains not found in the PCV7 vaccine continued to increase, which prompted researchers to emphasize the need for better pneumococcal vaccines. 

The 2010 introduction of PCV13 vaccine, adding six additional strains to the original PCV7, resulted in a further decline of invasive pneumococcal disease. However, PCV 13 vaccine has not been completely effective in eliminating vaccine-strain invasive pneumococcal disease and serious infections have persisted despite the licensing of a broader vaccine.       

In addition to the vaccine’s ineffectiveness in eliminating pneumococcal disease from all strains contained within the vaccine, non-vaccine type strains have also emerged in the United States, most notably strains 33F, 22F, 12, 15B, 15C, and 23 A.  Other countries have experienced a similar situation, including Taiwan, which noted a decrease in vaccine-type strain invasive disease and confirmed pneumococcal disease but an increase in non-vaccine type strain invasive disease, most notably caused by strains 23A, 15A and 15B. 

Korea has also reported high rates of antibiotic-resistant strains not found in PCV13 since the introduction of the vaccine.  Non-vaccine type strains continue to appear in many Western European countries, prompting researchers to stress the need for new vaccines to cover the antibiotic-resistant strains of S. pneumoniae not found within the current vaccines.     

Researchers in the United States have noted that while invasive pneumococcal disease has decreased since the introduction of pneumococcal conjugate vaccines, S. pneumoniae strains have continued to adapt and this has resulted in the ongoing emergence of antibiotic resistant non-vaccine serotypes. 

The use of pneumococcal conjugate vaccines has also caused an increase in other serious pathogens such as Haemophilus influenzae and Moraxella catarrhalis. Since the introduction of PCV vaccines, H. influenzae and M. catarrhalis otitis media have increased to replace S.pneumoniae otitis media. 

While the CDC and other global health organizations have attributed the decrease in invasive pneumococcal disease to vaccination, the introduction of pneumococcal conjugate vaccines has brought changes to clinical practice. Emergency room collection of blood cultures, once a routine practice in the assessment and treatment of children presenting with fever in the emergency room, have decreased since PCV vaccine introduction.   This change in clinical treatment protocol may be obscuring the ability to detect vaccine and non-vaccine strains of pneumococcal disease in children. 

A study of Aboriginals living in Western Australia found that while PCV7 vaccination decreased the number of vaccine-type invasive pneumococcal infections in the elderly and young children, it significantly increased the amount of non-vaccine type pneumococcal diseases in adults. 

Another study involving a similar population in Australia found that vaccine strain pneumococcal disease was not replaced by non-vaccine strain disease in children but non-vaccine strain disease rose significantly in adults. This offset any potential benefit that vaccination might have had on the adult population. 

At the CDC’s October 2018 ACIP meeting, public health officials reported that vaccinating all persons 65 and older with PCV13 has had no impact on reducing the rates of both invasive and non-invasive pneumococcal disease.  In June 2019, ACIP voted to pull back from its 2014 routine recommendation and stated that healthy seniors 65 and older could consider vaccination with PCV13 after discussions with their physician. PCV13 was still recommended for seniors 65 years and older who have chronic health conditions and a single dose of PPSV23 was still recommended for all persons 65 and older. 

The continued emergence of non-vaccine types pneumococcal strains prompted the development of new pneumococcal vaccines. Merck received FDA approval in July 2021 for a 15-valent pneumococcal vaccine, PCV15, for use in adults 18 years and older   This vaccine adds strain 22F and 33F to the 13 strains currently found in PCV13.  In June 2022, the FDA approved use of PCV15 for individuals six weeks of age and older. 

Pfizer (Wyeth) was awarded Breakthrough Therapy Designation by the FDA for a new 20-valent pneumococcal vaccine in September 2018.  Breakthrough Therapy Designation allows drug companies the opportunity to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).  On June 10, 2021, the FDA approved Prevnar 20 (PCV20) for use in adults 18 and older.  PCV20 adds strains 8, 10A, 11A, 12F, 15B, 22F, 33F to the 13 strains found in PCV13. 

On October 20, 2021, ACIP voted to recommend that all adults 65 years of age and older who have not previously received a dose of pneumococcal conjugate vaccine be given a dose of PCV15 or PCV20. If PCV15 is administered, the CDC recommended that a dose of PPSV23 be given, at least one year after PCV15. The interval, however, could be shortened to eight weeks in persons who are immunocompromised.  Persons 19 through 64 years with pre-existing health conditions that put them at an increased risk of invasive pneumococcal disease and who had not previously received a dose of pneumococcal conjugate vaccine were also recommended vaccination with PCV15 or PCV20. For individuals who received a dose of PCV15, a dose of PPSV23 was also recommended, to be given at least one year apart. 

In all clinical trials, the immune responses to PCV15 and PCV20 were reported to be non-inferior to PCV13. There are, however, no established corelates of protection that ensure an individual is protected from invasive pneumococcal disease.   

PCV15 and PCV20 were developed to target additional pneumococcal strains not covered by PCV13 but there is a lack of clinical data to determine whether PCV15 and PCV20 will prevent invasive pneumococcal disease caused by the strains targeted by these vaccines.    Additionally, while the CDC is recommending use of PCV20 vaccine for children with risk factors for pneumococcal disease, there is a lack of clinical data to support this recommendation since clinical trials did not involve high-risk children. 

CAPVAXIVE (PCV21), manufactured by Merck, was approved by the FDA through an accelerated approval process, in June 2024. According to the manufacturer, in adults 50 years and older, PCV21 targets approximately 84 percent of the pneumococcal serotypes associated with invasive pneumococcal disease (IPD) and 85 percent of serotypes associated with IPD in adults 65 years and older. 

Clinical trials of PCV21 did not study the vaccine’s efficacy or effectiveness. Like with other pneumococcal conjugate vaccines, immune responses (immunogenicity) were measured and compared against other licensed vaccines. PCV21 compared immune responses to those of PCV20, and were reported by Merck to be non-inferior in the 10 serotypes contained in both vaccines, and superior in 10 of the 11 serotypes unique to PCV21.  There are, however, no established corelates of protection that ensure an individual is protected from invasive pneumococcal disease.

No data is available on whether PCV21 will have any impact on the rates of invasive pneumococcal disease in adults.