Adventures In Vaccine Reactions – Revisited

 

Component	PNEUMOVAX 23 (Pneumococcal Vaccine Polyvalent, PPSV23)	Prevnar 20 (Pneumococcal 20-valent Conjugate Vaccine, PCV20)	References
Antigens (type)	Purified unconjugated capsular polysaccharides	Capsular saccharides individually conjugated to carrier protein (glycoconjugates)	1, 2, 4
Serotypes	23 serotypes: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F	20 serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 33F	1, 2
Antigen quantity per 0.5 mL	25 µg of each polysaccharide	~2.2 µg of each saccharide, except 4.4 µg of 6B	1, 2
Carrier protein	None (unconjugated)	CRM197 (non-toxic diphtheria toxin variant), ~51 µg	1, 2, 3
Adjuvant	None	Aluminum phosphate, 125 µg aluminum	1, 2, 3
Preservative	0.25% phenol	None	1, 2
Buffer/surfactant/salt (inactive)	Isotonic saline solution	Polysorbate 80 (100 µg), succinate buffer (295 µg), sodium chloride (4.4 mg)	1, 2, 3
Formulation	Clear, colorless solution; ready to use (no reconstitution)	Sterile suspension; ready to use	1, 2
Route	Intramuscular or subcutaneous	Intramuscular only	1, 3
Latex	Vial/syringe components not made with natural rubber latex	Not specified in retrieved label	2
1:  Prevnar 20.  FDA Package Insert.  2021:  https://www.fda.gov/vaccines-blood-biologics/vaccines/prevnar-20 2:  Pneumovax 23.  FDA Package Insert.  2021: https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-PNEUMOVAX-23_0.pdf 3:  Kobayashi M, Pilishvili T, Farrar JL, Leidner AJ, Gierke R, Prasad N, Moro P, Campos-Outcalt D, Morgan RL, Long SS, Poehling KA, Cohen AL. Pneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023. MMWR Recomm Rep. 2023 Sep 8;72(3):1-39. doi: 10.15585/mmwr.rr7203a1. PMID: 37669242; PMCID: PMC10495181. 4:  Two New Pneumococcal Vaccines-Prevnar 20 and Vaxneuvance. JAMA. 2021 Dec 28;326(24):2521-2522. doi: 10.1001/jama.2021.22119. PMID: 34962532.

 

 I saw my primary care MD yesterday and got the Prevnar Pneumococcal vaccine.  They had offered it to me last October but given the reaction to a previous injection Pneumovax 23 – I decided to hold off an do more research.  Everything I could find suggested that this was a new vaccine and a severe local reaction was not a contraindication to further pneumococcal vaccines.  I have seen and treated people with both pneumococcal pneumonia and meningitis and wanted to decrease the chances of getting either condition. They both have significant mortality rates and the patient I treated for meningitis survived but was completely deaf as a complication of the infection.

I have had anaphylactic reactions to anti-rabies Duck embryo vaccine.  That was not a modern vaccine and have since had newer versions of anti-rabies vaccines without complications.  As a precaution, the nurse who administered the shot told me to hang around in the clinic for 15 or 20 minutes before leaving.  I also had a history of not getting the influenza vaccine for 20 years based on that duck embryo allergy designation.  After seeing several fatalities from influenza including one in a young very physically fit man – I saw an allergist who said: “If you can eat eggs - I would not worry.”  I have been getting the influenza vaccines every year since and have had no problems with it.   Great advice from that allergist/immunologist.

I am naturally interested in why one pneumococcal vaccination caused such a reaction and the other did not.  I constructed the table for comparison. In terms of design, both use capsular saccharides or polysaccharides – the main difference being Prevnar 20 conjugates (or attaches) them to a carrier protein CRM197. Polysaccharides alone lead to a T-cell independent response that produces antibodies but no memory B cells.  The conjugated polysaccharides in Prevnar 20 produce a T-cell dependent response with memory B. cells.  That mechanism is thought to be encapsulation by T-cells and intermittent presentation of the antigen to external B-cells.   

The other significant difference is in the total amount of antigen injected at the immunization site.  For Pneumovax that is 23 antigens x 25 mcg/antigen or 575 mcg total.  For Prevnar that is 19 antigens x 2.2 mcg/antigen + 4.4 mcg or 46.2 mcg total.  So there is a much larger deposit of antigenic material at the immunization site for Pneumovax.  That may also be the reason why Pneumovax does not require an adjuvant.

The remaining differences seem trivial and are not likely to explain the difference in localized vaccine reactions. If something changes in the next few days, I will correct this post but at this time it seems unlikely.  In this case there is a clear explanation for the difference in vaccine reactions in a patient with multiple allergies and a history of an anaphylactic reaction to some vaccines.

In this era of vaccine controversies, I thought it was important to make the point that a reaction from one vaccine does not mean you can’t take another one.  It is more confusing when they have the same indication and it is the next shot in a series.  This example also illustrates that a local reaction, even if it is fairly severe does not mean there will be a systemic reaction like anaphylaxis. Analyzing what happens if you have a reaction is necessary because vaccines are that important.  In my case, I have an excellent internal medicine specialist who knew this would not be a problem.  If there is any doubt – allergists and immunologists are available for second opinions.

 

George Dawson, MD, DFAPA