Q:

3/5/2013
My question has to do with the use of Prevnar 13 in patients with specific pneumococcal antibody deficiency. Summary statement 31 from the practice parameter of diagnostic vaccination states that PCV13 can be administered to patients who have poor response to PPV23. I think there are recommendations from the CDC to give the PCV13 1st and then wait 2 months to give PPV23 as opposed to the reverse order. However, one cannot make a diagnosis of specific antibody deficiency until PPP23 is given. My specific question is whether to give PCV13 in patients with specific antibody deficiency if so, when should it be given in relationship to PPV23.

A:

Thank you for your inquiry.

To clarify the issues you are inquiring about, and for the sake of our readers, I have copied below selected quotes from both the Practice Parameter and the CDC statement to which you refer.

I believe that your statement regarding the preferred administration of PCV13 before PPSV23 is based on the quote below taken from the CDC document “Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine for Adults with Immunocompromising Conditions: Recommendations of the Advisory Committee on Immunization Practices (ACIP).” For your convenience, I have also placed a direct link to this document below. I have bolded the section from which I think the conclusion that PCV13 should be administered first is derived.

However, if one reads further in that document (see “Previous Vaccination with PPSV23”), you can see that if a patient has been immunized with PPSV23, one can proceed with immunization using PCV13, and the optimal time for this administration depends on whether or not the patient needs additional doses of PPSV23 to complete the immunization schedule..

Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine for Adults with Immunocompromising Conditions: Recommendations of the Advisory Committee on Immunization Practices (ACIP)

"Four studies of PCV7 immunogenicity involving 699 HIV-infected subjects, all with CD4 counts of >200 cells/µL, were conducted in the United States and Europe. Antibody response to a single dose of PCV7 was comparable with PPSV23 for the serotypes evaluated, at all times studied (10–13). When PPSV23 and PCV7 were administered in series, greater immune response was demonstrated when PCV7 was given first (8,11). None of the studies were designed to evaluate the optimal interval between doses; however, in another study, no evidence of blunting of an immune response to PCV7 was observed when a dose of PPSV23 was given 5 years (range: 3.5–6.6 years) before a dose of PCV7 (14)."

ACIP Recommendations for PCV13 and PPSV23 Use

"Adults with specified immunocompromising conditions who are eligible for pneumococcal vaccine should be vaccinated with PCV13 during their next pneumococcal vaccination opportunity."

Pneumococcal vaccine-naïve persons. "ACIP recommends that adults aged ≥19 years with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, and who have not previously received PCV13 or PPSV23, should receive a dose of PCV13 first, followed by a dose of PPSV23 at least 8 weeks later (Table). Subsequent doses of PPSV23 should follow current PPSV23 recommendations for adults at high risk. Specifically, a second PPSV23 dose is recommended 5 years after the first PPSV23 dose for persons aged 19–64 years with functional or anatomic asplenia and for persons with immunocompromising conditions. Additionally, those who received PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years, or later if at least 5 years have elapsed since their previous PPSV23 dose."

Previous vaccination with PPSV23. "Adults aged ≥19 years with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, who previously have received ≥1 doses of PPSV23 should be given a PCV13 dose ≥1 year after the last PPSV23 dose was received. For those who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and at least 5 years after the most recent dose of PPSV23.”

Next, I would like to turn to the Practice Parameter (see quotes below) mentioned in your inquiry. I have included, in addition to Summary Statement 31 to which you referred, Summary Statements 17 and 29.

My interpretation of Summary Statement 31 is that it is referring to the use of PCV13 as a diagnostic measure to see if a patient would preferentially respond to a protein antigen. I did not take this statement to refer to the use of PCV13 as an immunizing agent per se.

In Summary Statement 17, it notes that “It is important for the prescribing provider to be familiar with the FDA-approved indications for these vaccines because some uses might represent an “off-label” indication.” I think that this turns your attention back to the previously stated paragraph in the Advisory Committee on Immunization Practices (ACIP) detailing the optimal times of administration of PCV13 in a patient who has received PPSV23.

As an aside, you can see that patients who have previously received PCV7 or PCV13 can be given PPSV23 as well in Summary Statement 29 of the Parameters.

In conclusion, in the therapeutic administration of PCV13 to a patient who has been previously immunized with PPSV23, optimally one would follow the recommendations of the ACIP noted above. But PCV13 can also be used to determine whether a patient would preferentially respond to a protein antigen as a diagnostic measure as well.

Thank you again for your inquiry and we hope this response is helpful to you.

Summary Statement 17: PCV7 and PCV13 are used occasionally in the diagnosis of immunodeficiency. (IIb C)

PCV7 or PCV13 can also be used in subjects older than 2 years (including adults) with a poor response to PCV23 to determine their response to protein-conjugate antigen.73, 74 A single dose is recommended.58 For immunodeficient HIV-infected adults, 2 doses 1 month apart were used.81 It is important for the prescribing provider to be familiar with the FDA-approved indications for these vaccines because some uses might represent an “off-label” indication.

Summary Statement 29: Patients who have previously received PCV7 or PCV13 can be given PPV23. (III C)

Previous administration of PCVs does not preclude the subsequent administration of PPV23. Immunization with PPV23 can increase the titers of the PCV7 or PCV13 strains, as well as immunize against the strains not present in PCV vaccines.76, 79 However, it was observed in subjects older than 70 years of age that an initial dose of 23-valent PPV led to decreased response to the 7-valent PCV. The same type of observation was made with meningococcal polysaccharide vaccine,90 and these results are discussed elsewhere in this document. A poor response to PPV23 in this situation in a patient who has had a good response to PCV, however, is suggestive of an SAD.

Summary Statement 31: PCV7 or PCV13 protein conjugate vaccines can be administered to patients who have a poor response to PPV23. (III C)

A response to PCV suggests that the subject is able to respond preferentially to protein antigens but does not alter the diagnosis of selective antibody deficiency.91, 92 PPV vaccination can boost the preexisting antibody response to the serotypes present in the PCV vaccine.73, 74

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology