Q:

9/13/2013
If adult patient with frequent sinusitis and bronchitis has normal response to tetanus, diphtheria, poor response to pneumovax and borderline IgG (high 500's) do you always give prevnar to see if you can get a response? Also the company states you should wait one year after pneumovax to give prevnar, do you adhere to this recommendation or give it sooner?

A:

Thank you for your inquiry.

There is no clear-cut evidence-based or consensus answer to your question. There are two fairly recently published documents that deal with the issue you posed; that is, when and if to administer conjugated pneumococcal vaccine to a patient who has a blunted response to unconjugated pneumococcal vaccine.

One of these references is by Mark Ballow and is entitled “Use of vaccines in the evaluation of presumed immunodeficiency” published in the Annals of Allergy, Asthma, and Immunology 2013 (September), 111(3):163-166. The other reference is Jordan S. Orange, et al., “Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma, and Immunology, published in The Journal of Allergy and Clinical Immunology 2012 (September); 130(3) supplement:S1-S24.

In both of these articles, it is clear that an adult with a blunted response to unconjugated pneumococcal vaccine can receive the conjugated vaccine to further assess their response to help make a decision as to whether or not immunoglobulin replacement therapy is indicated. However, there is no clear-cut statement as to when (related to the first immunization) this second immunization should be given. The reason for some concern in this regard, and probably the reason that the manufacturer suggests a one year delay, is that repeat immunization can result in hyporesponsiveness. This is mentioned in both of the articles cited above.

Thus, we have in one instance, based upon the package insert, an interval of a year, and as you can see below in a quote from Dr. Ballow’s article, he sometimes administers both vaccines simultaneously. Also, in the Parameters, edited by Dr. Orange, it mentions that “for immunodeficient HIV-infected adults, two doses one month apart were used.”

For your convenience, I have directly copied quotes (see below) from these two documents that pertain to your inquiry.

In summary, I cannot give you a definite answer as to when the best time would be to administer the conjugated vaccine to your patient - but, we have personally been using an interval of one month.

The question as to who should receive a second immunization for diagnostic reasons is perhaps even difficult. I don't routinely give a second immunization, employing it only when the patient does not have a clear cut need for immunoglobulin replacement (eg no findings of chronic bacterial infection in the respiratory tract) but a poor response to Pneumovax.

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

“A common question is whether subsequent administration of a vaccine is contraindicated. Development of hyporesponsiveness in adults after repeated polysaccharide immunization has been reported for both pneumococcal polysaccharide vaccines12 and unconjugated meningococcal polysaccharide vaccines.13 In our own practice, we have generally waited at least 1 year before repeat administration of a booster immunization with the 23vPPV in children. Several studies have found that the prior administration of a conjugated pneumococcal polysaccharide vaccine can prime the response to the unconjugated purified pneumococcal polysaccharide vaccine.[9], [14] This priming effect is serotype specific in that serotypes not in the conjugate vaccine (PCV13) are not affected. This observation has led in our own practice to children being evaluated for selective antibody deficiency to administer both the 23vPPV and PCV13 at the same time to try to optimize the response, although we do not have any data to confirm this approach. Nevertheless, it does save time in the process of evaluation for the decision of using replacement immunoglobulin therapy. If the vaccine responses to both vaccines (unconjugated and conjugated serotypes) are not sufficient, it makes the decision for a trial of immunoglobulin therapy easier and more robust.”

Source:
Annals of Allergy, Asthma & Immunology, Volume 111, Issue 3 , Pages 163-166, September 2013.

Summary Statement 28: Immediate repeat booster doses of PPV are ineffective (and not recommended and might promote hyporesponsiveness). (Ib B)

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

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

Previously PCV7 and now PCV13 can be used in infants and children less than 60 months of age who lack protective antibody titers to the pneumococcal serotypes contained in these vaccines. Three immunizations are recommended for children less than 24 months of age, and a single immunization is recommended for children 25 to 60 months of age or adults.58 These vaccines can be used in addition to the usual vaccine antigens used for the determination of T-dependent antibody response, such as tetanus toxoid, diphtheria toxoid, and conjugated H influenzae vaccines.4

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 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”

Source:
The Journal of Allergy and Clinical Immunology, Volume 130, Issue 3, Supplement, Pages S1-S24, 2012

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology