Pneumonia Vaccination Is More Complex but Better Than Ever

In my 30+ years as a family physician I’ve seen first hand the effects of a relatively new type of vaccines called conjugate polysaccharide vaccinations. In the 1980’s nearly every year I had one or more young children in the hospital with meningitis due to either Hemophyllus influenza B or Streptococcus pneumoniae.  Now there are both very uncommon. I don’t remember a case in my practice in the last 15 years. The latest ACIP recommendations for vaccination of adults for pneumonia are also the result of more research on conjugate vaccines.  Finally adults may get to benefit from this vaccination technology too. The ACIP in August changed their recommendations for immunization against pneumococcal pneumonia.

175,000 Americans get pneumonia annually with Strep. pneumonia, the most common cause of bacterial pneumonia.  This is often preventable by a vaccine that is recommended for those at highest risk, namely people over age 65, or people with various chronic diseases.  Recent information has led to a major change in the recommendation for pneumonia vaccination of adults. The new vaccine recommendation gives better protection, but requires two different types of pneumococcal pneumonia vaccination.

The new recommendations are the result of many factors and are a nice way to look at how epidemiologists and public health experts analyze data and make decisions.  For those of you who find this type of thing interesting read the summary of their thought processes and the studies they reviewed below.  Others may just want to skip to the recommendations.

Streptococcus pneumonia, often called “pneumococcus,” is the bacteria that causes the most common serious cases of pneumonia outside hospitals in the U.S.  Historically it has also been the most common cause of ear infections in children, bacterial meningitis and sinusitis.  There are many dozens of different strains of pneumococcus differentiated by them having different polysaccharide molecules in their outer membrane.  In 1977 a polysaccharide vaccine against 14 common strains of the pneumococcus was recommended for adults at high risk of pneumococcal pneumonia.  In 1983 it was expanded to cover 23 strains. This vaccine is contains polysaccharide components of these strains of pneumococcus and the immune response the immune response is primarily an IgM antibody response by B-lymphocytes.  This type of antibody response tends to be relatively short acting, does not elicit a memory response on getting future doses and requires a mature and robust immune system.  It does not consistently generate an immune response in children under 2 years old, the highest risk population of all. In 2000 a different type of vaccine called a conjugated vaccine.

Scientists have found that when the polysaccharide capsule proteins are conjugated (attached chemically) to certain proteins the immune response is much more vigorous, with higher antibody levels of more effective types of antibody, in addition to being longer lasting, having a “memory” feature allowing booster shots to create even stronger immunity. The reason for the different immune response is because the protein-polycaccharide conjugate induces an immune response using both T-cells and B-cells and produces memory cells specific to the polysaccharide of the variouus pneumococcal bacterial strains. Conjugate vaccines have been found effective in young children and  older adults whose immune system is less robust.

The first widely used conjugate vaccine in children was the HIB (Hemophyllus influenza B) vaccine. It was so effective that H. influenza B has gone from being the most common cause of fatal meningitis in young children to a very rare cause since the vaccine use became routine. Prior to routine HIB vaccination about 20,000 cases of invasive HIB  disease occurred annually in the US and 1000 deaths occurred.  By 2006 only 29 cases of invasive HIB disease were reported in the U.S. This tremendous success against HIB led to consideration of a conjugate vaccine against pneumococcus. A conjugate type vaccine is also used against the Nisseria meninigiditis bacteria that causes meningitis in older adolescents and young adults, and has been found to be very effective.

 

Polysaccharides are a large type of glycoprotein on the capsule of many bacteria. Immune response to these polysaccharides used alone  is very specific to the bacterial strains, but in young children or in some older adults the immune response is weak and short lived.  The initial study of the 7-valent pneumococcal conjugate vaccine in children done in 1998 by Kaiser Permenante in California suggested that the conjugate pneumococcal vaccine was 100% effective in a large-scale double-blinded controlled study.   Twenty-three cases of invasive pneumococcal disease in the study population led the study leaders to break the blinding of study participants.  All 23 of the cases were in the control group, and zero cases were in the actively immunized group.  This led to routine immunization of infants with pneumococcal PCV-7 beginning in 2000, and expanded to cover an additional 6 strains of pneumococcus as PCV-13 in 2010.  Since conjugate pneumococcal vaccine use became routine the incidence of invasive pneumococcal disease in children has dropped by about 80%

The other major population where Pneumovax, the 23 valent polysaccharide vaccine, is less effective is in older adults.  As we age our immune response to polysaccharide vaccines wanes.  The great success of PCV-13 in children led to study of this vaccine in adults.  These studies showed that conjugate vaccine has the benefit of improved immuinity compared to polysaccharide vaccines in adults, but that up to 38% of cases of pneunmococcal pneumonia in older adults is caused by strains covered by the 23 valent polysaccharide vaccine but not included in the PCV-13. To get the best immunity requires getting both the PCV-13 conjugate vaccine and the 23-valent polysaccharide vaccine.

It has also been determined that the overall response to persons who receive both Prevnar (PCV-13)and Pneumovax (23 valent polysaccharide) is better if the Prevnar is given first. In order to get the best response to  the polysaccharide vaccine after getting Prevnar (PCV-13) waiting at least 6 months if needed.  This research and data analysis led the ACIP to a change in pneumonia vaccination recommendations for adults in August, 2014. In order to avoid inaccuracy I’ve copied the CDC recommendations for use of the two pneumococcal vaccines in adults below:

ACIP Recommendations for PCV13 and PPSV23 Use:

Both PCV13 and PPSV23 should be administered routinely in series to all adults aged ≥65 years

Pneumococcal vaccine-naïve persons. Adults aged ≥65 years who have not previously received pneumococcal vaccine or whose previous vaccination history is unknown should receive a dose of PCV13 first, followed by a dose of PPSV23. The dose of PPSV23 should be given 6–12 months after a dose of PCV13. If PPSV23 cannot be given during this time window, the dose of PPSV23 should be given during the next visit. The two vaccines should not be coadministered, and the minimum acceptable interval between PCV13 and PPSV23 is 8 weeks.

Previous vaccination with PPSV23. Adults aged ≥65 years who have previously received ≥1 doses of PPSV23 also should receive a dose of PCV13 if they have not yet received it. A dose of PCV13 should be given ≥1 year after receipt of the most recent PPSV23 dose. For those for whom an additional dose of PPSV23 is indicated, this subsequent PPSV23 dose should be given 6–12 months after PCV13 and ≥5 years after the most recent dose of PPSV23 (15).

Potential Time-Limited Utility of Routine PCV13 Use Among Adults ≥65 Years. The recommendations for routine PCV13 use among adults aged ≥65 years will be reevaluated in 2018 and revised as needed.

ACIP recommendations for routine use of PCV13 in adults aged ≥19 years with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leak, or cochlear implants remain unchanged (6).

Coadministration with Other Vaccines

Concomitant administration of PCV13 and trivalent inactivated influenza vaccine (TIV) has been demonstrated to be immunogenic and safe. PCV13 can be coadministered with TIV in an adult immunization program. However, a randomized double-blind trial found slightly lower pneumococcal serotype–specific geometric mean concentrations and lower proportion achieving at least a fourfold rise in hemagglutination inhibition assay titer for one of three influenza subtypes (influenza A[H3N2]) with PCV13 plus TIV compared with PCV13 alone or TIV alone among adults aged ≥65 years (16). Currently, no data are available on coadministration with other vaccines (e.g., tetanus, diphtheria, and acellular pertussis vaccine or zoster vaccine) among adults.

Precautions and Contraindications

Before administering PCV13, vaccination providers should consult the package insert for precautions, warnings, and contraindications. Vaccination with PCV13 is contraindicated in persons known to have a severe allergic reaction (e.g., anaphylaxis) to any component of PCV13 or PCV7 or to any diphtheria toxoid–containing vaccine.

For those who prefer a visual graphic view of these recommendations here is the CDC graphic:

The figure is a box illustrating sequential administration and recommended intervals for 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥65 years in the United States.

 

So if you are getting your flu shot this fall, see if you need a pneumonia vaccine also.  If you are over 65 most of you should get conjugated PCV-13 (Prevnar®) either with your flu shot or if you wish in a few months.

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