Influence of pre-existing hemagglutination inhibition titers against historical influenza strains on antibody response to inactivated trivalent influenza vaccine in adults 50–80 years of age

Figures & data

Table 1. Demographic characteristics and underlying high-risk diseases, overall and stratified by age

Characteristics	Overall n = 264 n (%)	Age 50–64 y n = 157 n (%)	Age 65–80 y n = 107 n (%)	P value
Site Marshfield Pittsburgh	149 (56.4) 115 (43.6)	82 (52.2) 75 (47.8)	67 (62.6) 40 (37.4)	0.100
Female	152 (57.6)	98 (62.4)	54 (50.5)	0.054
White race	210 (79.6)	121 (77.1)	89 (83.2)	0.227
Body Mass Index, Mean (SD)	32.4 (7.3)	32.3 (7.5)	32.6 (6.9)	0.806
High Risk Diseases
Diabetes	112 (42.4)	58 (36.9)	54 (50.5)	0.029
Chronic cardiac diseases	64 (24.2)	26 (16.6)	38 (35.5)	<0.001
Chronic pulmonary diseases	48 (18.2)	30 (19.1)	18 (16.8)	0.890
Other high risk diseases	73 (27.7)	34 (21.7)	39 (36.4)	0.002

Table 2. Hemagglutination-inhibition responses to 2011–2012 trivalent inactivated influenza vaccine antigens, overall and stratified by age group

	2011–2012 Influenza Vaccine Strain
Immunological response measure	H1N1 A/California/07/2009				H3N2 A/Perth/16/2009
	Overall n = 264	Age 50–64 y n = 157	Age 65–80 y n = 107	*P value	Overall n = 264	Age 50–64 y n = 157	Age 65–80 y n = 107	*P value
Seroprotection (HI titer ≥ 1:40) Day 0 (%)	36.7	38.2	34.6	0.55	28.4	31.9	23.4	0.13
Titer ³ 1:40 – Seroprotection Day 21 (%)	65.9	66.9	64.5	0.69	63.3	63.7	62.6	0.86
Seroconversion (4-fold rise at Day 21) (%)	33.7	33.1	34.6	0.81	37.5	35.7	40.2	0.46
GMT ratio (95% CI)	2.1 (1.9–2.5)	2.1 (1.8–2.5)	2.2 (1.8–2.7)	0.69	2.3 (2.0–2.6)	2.3 (1.9–2.7)	2.3 (1.9–2.8)	0.86
Adjusted GMT ratio^# (95% CI)	2.1 (1.9–2.4)	2.1 (1.8–2.5)	2.2 (1.8–2.7)	0.86	2.3 (2.0–2.6)	2.3 (1.9–2.7)	2.3 (1.9–2.8)	0.89

GMT, geometric mean titer; CI, confidence interval; Seroconversion, 4-fold rise in post vaccination titer; Seroprotected, HI titer ≥ 40. *Comparison of the 2 age groups. ^#Adjusted for sex, site, race group, and diabetes.

Table 3. Geometric mean titers for 2011–2012 influenza A vaccine and selected historical strains, overall and stratified by age

Vaccine Strain	Geometric Mean Titers Mean (95% CI)			*P value
	Overall (n = 264)	Age 50–64 y (n = 157)	Age 65–80 y (n = 107)
A(H1N1)
A/California/07/2009 Day 0	23.7 (21.1–26.7)	26.2 (22.1–31.0)	20.5 (17.6–23.9)	0.038
A/California/07/2009 Day 21	50.9 (44.5–58.2)	55.0 (45.8–65.9)	45.5 (37.5–55.4)	0.177
A/Puerto Rico/8/1934	21.9 (19.5–24.5)	16.8 (14.8–19.2)	32.1 (26.7–38.6)	<0.001
A/Fort Monmouth/1/1947	31.9 (28.4–35.9)	27.0 (23.2–31.4)	40.8 (34.1–48.7)	<0.001
A/Texas/36/1991	40.3 (35.2–46.2)	42.7 (35.7–51.1)	37.0 (29.9–45.8)	0.312
A/New Caledonia/20/1999	62.2 (54.7–70.7)	59.0 (49.7–70.1)	67.2 (55.4–81.4)	0.332
A/Solomon Islands/3/2006	27.8 (24.5–31.5)	32.4 (27.2–38.6)	22.2 (18.8–26.1)	0.004
A/Brisbane/59/2007	11.8 (11.3–12.4)	12.4 (11.5–13.3)	11.1 (10.4–11.8)	0.039
A(H3N2)
A/Perth/16/2009 Day 0	19.9 (17.8–22.3)	21.5 (18.4–25.1)	17.9 (15.4–20.9)	0.105
A/Perth/16/2009 Day 21	46.0 (40.2–52.5)	49.0 (41.2–58.3)	41.9 (34.0–51.5)	0.256
A/Sydney/5/1997	55.8 (48.5–64.3)	51.4 (42.7–62.0)	63.0 (51.0–78.0)	0.165
A/Panama/2007/1999	87.7 (77.2–99.6)	84.0 (71.1–99.2)	93.5 (76.6–114.0)	0.420
A/Fujian/411/2002	105.8 (92.8–120.6)	98.4 (82.7–117.2)	117.7 (96.5–143.4)	0.192
A/Wisconsin/67/2005	46.0 (40.1–52.7)	44.5 (36.9–53.6)	48.3 (39.8–58.6)	0.562
A/Brisbane/10/2007	41.5 (36.2–47.6)	42.4 (35.3–50.8)	40.3 (32.8–49.4)	0.720

GMT, geometric mean titer. *P value comparing the 2 age groups obtained by ANOVA for log-transformed titers.

Figure 1. Percent of participants with seroprotective (titer ≥ 1:40) at Day 0 to A(H1N1) and A(H3N2) influenza virus strains. The overall height of the bars indicates the percent of participants with seroprotective titers (HI ≥ 1:40) to a given historical strain at Day 0. The upper part of each bar indicates the percent of those individuals who seroconverted (≥4-fold rise in titer) against the specified current influenza vaccine A virus strain. *Difference in percent seroprotected between age groups (P < 0.05). A/PR/8/1934 = A/Puerto Rico/8/1934; A/FM/1/1947 = A/Fort Monmouth/1/1947; A/TX/36/1991 = A/Texas/36/1991; A/NC/1999 = A/New Caledonia/20/1999; A/SI/2006 = A/Solomon Islands/3/2006; A/Bris/59/2007 = A/Brisbane/59/2007; A/CA/07/2009 = A/California/07/2009; A/Syd/5/1997 = A/Sydney/5/1997; A/Pan/2007/99 = A/Panama/2007/1999; A/Fuj/411/2002 = A/Fujian/411/2002; A/Wis/67/2005 = A/Wisconsin/67/2005; A/Bris/10/2007 = A/Brisbane/10/2007.

Figure 2. Proportion of participants with seroprotected (titers ≥ 1:40) at Day 21 by type and by the count of seropositive historical influenza strains among those seronegative at Day 0. The number of historical viruses for which each specimen had a titer ≥ 1:40 was called the “historical count”—for example, if a given serum specimen were tested against 6 historical viruses and had a titer ≥ 1:40 for 4 of them, the historical count was 4.

Table 4. Association of 2011–2012 influenza vaccine A strain seroprotection (HI titer ≥ 1:40) and seroconversion with count* of historical strains that have seroprotective titers (HI titer ≥ 1:40) at Day 0 from logistic regression: adjusted results

Row	Variable	2011–2012 Influenza A Vaccine Strains
		A(H1N1) Odds Ratio (95% CI)	A(H3N2) Odds Ratio (95% CI)
	Outcome: Pre-vaccination Day 0 Titers ≥ 1:40 vs. < 1:40
1	Count of seroprotective responses to historical strains	1.43 (1.17–1.75)	2.66 (1.95–3.64)
	Outcome: Post-vaccination Day 21 Seroprotective Titers ≥ 1:40 vs. < 1:40: Full Data Set
2	Day 0 2011–2012 strain titers ≥ 40 (ref. < 40) Day 0	8.46 (3.94–18.15)	6.28 (2.60–15.19)
3	Count of seroprotective responses to historical strains	1.28 (1.02–1.61)	1.34 (1.09–1.65)
	Outcome: Post-vaccination Day 21 Seroprotective Titers ≥ 1:40 vs. < 1:40: Restricted to Day 0 Vaccine Seronegatives
4	Count of seroprotective responses to historical strains	1.41 (1.09–1.82)	1.32 (1.07–1.62)
	Outcome: Seroconversion - 4-fold Rise in Day 21 Titers
5	Count of seroprotective responses to historical strains	1.20 (0.96–1.50)	1.24 (1.01–1.52)
6	log2 Day 0 2011–2012 strain titers	0.53 (0.41–0.69)	0.55 (0.42–0.72)

All models adjusted for age group, sex, race, site (Marshfield vs. Pittsburgh), and diabetes. CI, confidence interval. *The number of historical strains for which each specimen had a titer ≥ 1:40 for that type was called the “historical count”; for example, if a given serum specimen were tested against 6 historical A(H1N1) viruses and had a titer ≥1:40 for 4 of them, the historical count was 4 for A(H1N1).