Coadministration of 13-valent pneumococcal conjugate and quadrivalent inactivated influenza vaccines in adults previously immunized with polysaccharide pneumococcal vaccine 23: a randomized clinical trial

Figures & data

Figure 1. Subject disposition.

PCV13 = 13-valent pneumococcal conjugate vaccine; QIV = quadrivalent inactivated influenza vaccine. *1 subject reported colitis 19 days after vaccination 1 (not related to study vaccine); 1 subject experienced mild injection-site induration and pain (both vaccines) 1 day after vaccination 1, resolving after 31 days (related to study vaccines).

Table 1. Comparison of Pneumococcal OPA GMTs 1 Month After PCV13+ QIV vs 1 Month After PCV13 Alone (Evaluable Immunogenicity Population).

	Vaccine Sequence (as Randomized)
	PCV13+QIV, placebo		Placebo+QIV, PCV13		Vaccine Comparison
Serotype	n^a	GMT^b (95% CI)^c	n^a	GMT^b (95% CI)^c	Ratio^d (95% CI)^e
1	419	75 (65.0–87.0)	417	83 (71.1–96.1)	0.9 (0.74–1.12)
3	422	41 (36.2–46.0)	418	49 (43.6–55.3)	0.8 (0.70–0.98)
4	412	587 (489.9–702.5)	417	824 (692.2–980.0)	0.7 (0.55–0.91)
5	423	97 (83.8–111.7)	414	101 (86.6–117.2)	1.0 (0.78–1.18)
6A	420	953 (805.7–1126.3)	415	1413 (1203.3–1659.4)	0.7 (0.53–0.85)
6B	414	867 (722.3–1039.6)	405	1041 (860.5–1260.0)	0.8 (0.64–1.08)
7F	424	651 (582.4–728.0)	419	670 (599.7–748.5)	1.0 (0.83–1.14)
9V	419	699 (613.7–797.2)	415	838 (734.2–957.5)	0.8 (0.69–1.00)
14	421	574 (496.8–663.0)	416	760 (665.6–868.0)	0.8 (0.62–0.92)
18C	420	713 (598.9–849.9)	414	865 (726.4–1030.5)	0.8 (0.64–1.06)
19A	425	337 (294.9–384.6)	419	390 (344.4–441.1)	0.9 (0.72–1.04)
19F	423	324 (274.8–382.5)	416	360 (302.7–427.9)	0.9 (0.71–1.14)
23F	421	278 (223.9–344.7)	417	364 (294.3–451.3)	0.8 (0.56–1.03)

GMT = geometric mean titer; OPA = opsonophagocytic activity; PCV13 = 13-valent pneumococcal conjugate vaccine; QIV = quadrivalent inactivated influenza vaccine.

Underlined vaccine names indicate which immune response data for each study group are presented for comparison in the table.

^an = Number of subjects with a determinate OPA titer to the given serotype.

^bGMTs were calculated using all subjects with available data for the specified blood draw.

^cCIs are back-transformations of a CI based on the Student t distribution for the mean logarithm of the titers.

^dRatio of GMTs PCV13+QIV/placebo to placebo+QIV/PCV13 was calculated by back-transforming the mean difference between vaccine sequences on the logarithmic scale.

^eCIs for the ratio are back-transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (PCV13+QIV/placebo – placebo+QIV/PCV13).

Figure 2. Pneumococcal OPA titer reverse cumulative distribution curves before and 1 month after PCV13 administration.

PCV13 = 13-valent pneumococcal conjugate vaccine; QIV = quadrivalent inactivated influenza vaccine. Reverse cumulative distribution curves displaying pneumococcal OPA titers for PCV13 serotypes before (solid lines) and after (dotted lines) PCV13 immunization are shown (evaluable immunogenicity population). Black line, PCV13+QIV/placebo; gray line, placebo+QIV/PCV13. Vertical line, OPA lower limit of quantitation titers for each serotype.

Table 2. Comparison of Influenza HAI GMTs 1 Month After PCV13+QIV vs Placebo+QIV (Evaluable Immunogenicity Population).

	Vaccine Sequence (as Randomized)
	PCV13+QIV, placebo n^a = 427	Placebo+QIV, PCV13 n^a = 430	Vaccine Comparison
Strain	GMT^b (95% CI)^c	GMT^b (95% CI)^c	Ratio^d (95% CI)^e
A/H1N1	115 (104.0–126.8)	113 (101.6–124.7)	1.0 (0.88–1.18)
A/H3N2	226 (206.1–248.5)	196 (178.0–216.1)	1.2 (1.01–1.32)
B/Brisbane	28 (25.7–31.0)	26 (23.7–28.7)	1.1 (0.95–1.24)
B/Massachusetts	45 (41.0–50.3)	43 (39.1–48.2)	1.0 (0.90–1.21)

GMT = geometric mean titer; HAI = hemagglutination inhibition assay; PCV13 = 13-valent pneumococcal conjugate vaccine; QIV = quadrivalent inactivated influenza vaccine.

Underlined vaccine names indicate which immune response data for each study group are presented for comparison in the table.

^an = Number of subjects with a determinate HAI titer to the given strain.

^bGMTs were calculated using all subjects with available data for the specified blood draw.

^cCIs are back-transformations of a CI based on the Student t distribution for the mean logarithm of the titers.

^dRatio of GMTs PCV13+QIV/placebo to placebo+QIV/PCV13 was calculated by back-transforming the mean difference between vaccine sequences on the logarithmic scale.

^eCIs for the ratio are back-transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (PCV13+QIV/placebo – placebo+QIV/PCV13).

Table 3. Comparison of Seroconversion Rates of Influenza Strains Between PCV13+QIV and Placebo+QIV (Evaluable Immunogenicity Population).

	Vaccine Sequence (as Randomized)
	PCV13+QIV, placebo N^a = 427		Placebo+QIV, PCV13 N^a = 430
Strain	n^b	% (95% CI)^c	n^b	% (95% CI)^c	Difference^d (95% CI)^e
A/H1N1	125	29.3 (25.0–33.8)	104	24.2 (20.2–28.5)	5.1 (−0.9 to 11.0)
A/H3N2	119	27.9 (23.7–32.4)	136	31.6 (27.3–36.3)	−3.8 (−9.9 to 2.4)
B/Brisbane	91	21.3 (17.5–25.5)	96	22.3 (18.5–26.6)	−1.0 (−6.6 to 4.5)
B/Massachusetts	99	23.2 (19.3–27.5)	106	24.7 (20.6–29.0)	−1.5 (−7.2 to 4.3)

HAI = hemagglutination inhibition assay; PCV13 = 13-valent pneumococcal conjugate vaccine; QIV = quadrivalent inactivated influenza vaccine.

Underlined vaccine names indicate which immune response data for each study group are presented for comparison in the table.

^aN = Number subjects with known values.

^bn = Number of subjects with the given characteristic.

^cExact 2-sided CI (Clopper and Pearson) based on the observed proportion of subjects.

^dDifference in proportions (PCV13+QIV/placebo – placebo+QIV/PCV13) expressed as a percentage.

^eExact 2-sided CI and corresponding P value (based on Chan and Zhang) for the difference in proportions (PCV13+QIV/placebo – placebo+QIV/PCV13) expressed as a percentage.