Immunogenicity of a meningococcal B vaccine during a university outbreak

Nicole E. Basta, Adel A F Mahmoud, Julian Wolfson, Alexander Ploss, Brigitte L. Heller, Sarah Hanna, Peter Johnsen, Robin Izzo, Bryan T. Grenfell, Jamie Findlow, Xilian Bai, Ray Borrow

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Abstract

BACKGROUND: In December 2013, a multicomponent meningococcal serogroup B (4CMenB) vaccine was used before licensure on the basis of special consideration by the Food and Drug Administration to respond to an outbreak of Neisseria meningitidis B at a U.S. university. Data suggested that vaccination would control the outbreak because isolates expressed antigens that were closely related to the vaccine antigens (factor H-binding protein [fHbp] and neisserial heparin-binding antigen). We quantified the immune responses induced by 4CMenB during the outbreak. METHODS: We conducted a seroprevalence survey among students to assess vaccination status and collect serum specimens to quantify titers of serum bactericidal antibodies (SBA) with an assay that included human complement (hSBA). We compared the proportion of vaccinated and unvaccinated participants who were seropositive for the outbreak strain and for one closely related reference strain (44/76-SL, which included fHbp) and one mismatched reference strain (5/99, which included neisserial adhesin A), both of which were used in vaccine development. Seropositivity was defined as an hSBA titer of 4 or higher. RESULTS: Among the 499 participants who received two doses of the 4CMenB vaccine 10 weeks apart, 66.1% (95% confidence interval [CI], 61.8 to 70.3) were seropositive for the outbreak strain, although the geometric mean titer was low at 7.6 (95% CI, 6.7 to 8.5). Among a random subgroup of 61 vaccinees who also received two doses but did not have a detectable protective response to the outbreak strain, 86.9% (95% CI, 75.8 to 94.2) were seropositive for the 44/76-SL strain, for which there was a geometric mean titer of 17.4 (95% CI, 13.0 to 23.2), whereas 100% of these vaccinees (95% CI, 94.1 to 100) were seropositive for the 5/99 strain and had a higher geometric mean titer (256.3; 95% CI, 187.3 to 350.7). The response to the outbreak strain was moderately correlated with the response to the 44/76-SL strain (Pearson's correlation, 0.64; P<0.001) but not with the response to the 5/99 strain (Pearson's correlation, -0.06; P = 0.43). CONCLUSIONS: Eight weeks after the second dose of the 4CMenB vaccine was administered, there was no evidence of an hSBA response against the outbreak strain in 33.9% of vaccinees, although no cases of meningococcal disease caused by N. meningitidis B were reported among vaccinated students.

Original languageEnglish (US)
Pages (from-to)220-228
Number of pages9
JournalNew England Journal of Medicine
Volume375
Issue number3
DOIs
StatePublished - Jul 21 2016

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Meningococcal Vaccines
Disease Outbreaks
Confidence Intervals
Complement Factor H
Neisseria meningitidis
Antigens
Serum Bactericidal Antibody Assay
Vaccination
Vaccines
Students
Seroepidemiologic Studies
United States Food and Drug Administration
Licensure
Carrier Proteins

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Immunogenicity of a meningococcal B vaccine during a university outbreak. / Basta, Nicole E.; Mahmoud, Adel A F; Wolfson, Julian; Ploss, Alexander; Heller, Brigitte L.; Hanna, Sarah; Johnsen, Peter; Izzo, Robin; Grenfell, Bryan T.; Findlow, Jamie; Bai, Xilian; Borrow, Ray.

In: New England Journal of Medicine, Vol. 375, No. 3, 21.07.2016, p. 220-228.

Research output: Contribution to journalArticle

Basta, NE, Mahmoud, AAF, Wolfson, J, Ploss, A, Heller, BL, Hanna, S, Johnsen, P, Izzo, R, Grenfell, BT, Findlow, J, Bai, X & Borrow, R 2016, 'Immunogenicity of a meningococcal B vaccine during a university outbreak', New England Journal of Medicine, vol. 375, no. 3, pp. 220-228. https://doi.org/10.1056/NEJMoa1514866
Basta, Nicole E. ; Mahmoud, Adel A F ; Wolfson, Julian ; Ploss, Alexander ; Heller, Brigitte L. ; Hanna, Sarah ; Johnsen, Peter ; Izzo, Robin ; Grenfell, Bryan T. ; Findlow, Jamie ; Bai, Xilian ; Borrow, Ray. / Immunogenicity of a meningococcal B vaccine during a university outbreak. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 3. pp. 220-228.
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abstract = "BACKGROUND: In December 2013, a multicomponent meningococcal serogroup B (4CMenB) vaccine was used before licensure on the basis of special consideration by the Food and Drug Administration to respond to an outbreak of Neisseria meningitidis B at a U.S. university. Data suggested that vaccination would control the outbreak because isolates expressed antigens that were closely related to the vaccine antigens (factor H-binding protein [fHbp] and neisserial heparin-binding antigen). We quantified the immune responses induced by 4CMenB during the outbreak. METHODS: We conducted a seroprevalence survey among students to assess vaccination status and collect serum specimens to quantify titers of serum bactericidal antibodies (SBA) with an assay that included human complement (hSBA). We compared the proportion of vaccinated and unvaccinated participants who were seropositive for the outbreak strain and for one closely related reference strain (44/76-SL, which included fHbp) and one mismatched reference strain (5/99, which included neisserial adhesin A), both of which were used in vaccine development. Seropositivity was defined as an hSBA titer of 4 or higher. RESULTS: Among the 499 participants who received two doses of the 4CMenB vaccine 10 weeks apart, 66.1{\%} (95{\%} confidence interval [CI], 61.8 to 70.3) were seropositive for the outbreak strain, although the geometric mean titer was low at 7.6 (95{\%} CI, 6.7 to 8.5). Among a random subgroup of 61 vaccinees who also received two doses but did not have a detectable protective response to the outbreak strain, 86.9{\%} (95{\%} CI, 75.8 to 94.2) were seropositive for the 44/76-SL strain, for which there was a geometric mean titer of 17.4 (95{\%} CI, 13.0 to 23.2), whereas 100{\%} of these vaccinees (95{\%} CI, 94.1 to 100) were seropositive for the 5/99 strain and had a higher geometric mean titer (256.3; 95{\%} CI, 187.3 to 350.7). The response to the outbreak strain was moderately correlated with the response to the 44/76-SL strain (Pearson's correlation, 0.64; P<0.001) but not with the response to the 5/99 strain (Pearson's correlation, -0.06; P = 0.43). CONCLUSIONS: Eight weeks after the second dose of the 4CMenB vaccine was administered, there was no evidence of an hSBA response against the outbreak strain in 33.9{\%} of vaccinees, although no cases of meningococcal disease caused by N. meningitidis B were reported among vaccinated students.",
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T1 - Immunogenicity of a meningococcal B vaccine during a university outbreak

AU - Basta, Nicole E.

AU - Mahmoud, Adel A F

AU - Wolfson, Julian

AU - Ploss, Alexander

AU - Heller, Brigitte L.

AU - Hanna, Sarah

AU - Johnsen, Peter

AU - Izzo, Robin

AU - Grenfell, Bryan T.

AU - Findlow, Jamie

AU - Bai, Xilian

AU - Borrow, Ray

PY - 2016/7/21

Y1 - 2016/7/21

N2 - BACKGROUND: In December 2013, a multicomponent meningococcal serogroup B (4CMenB) vaccine was used before licensure on the basis of special consideration by the Food and Drug Administration to respond to an outbreak of Neisseria meningitidis B at a U.S. university. Data suggested that vaccination would control the outbreak because isolates expressed antigens that were closely related to the vaccine antigens (factor H-binding protein [fHbp] and neisserial heparin-binding antigen). We quantified the immune responses induced by 4CMenB during the outbreak. METHODS: We conducted a seroprevalence survey among students to assess vaccination status and collect serum specimens to quantify titers of serum bactericidal antibodies (SBA) with an assay that included human complement (hSBA). We compared the proportion of vaccinated and unvaccinated participants who were seropositive for the outbreak strain and for one closely related reference strain (44/76-SL, which included fHbp) and one mismatched reference strain (5/99, which included neisserial adhesin A), both of which were used in vaccine development. Seropositivity was defined as an hSBA titer of 4 or higher. RESULTS: Among the 499 participants who received two doses of the 4CMenB vaccine 10 weeks apart, 66.1% (95% confidence interval [CI], 61.8 to 70.3) were seropositive for the outbreak strain, although the geometric mean titer was low at 7.6 (95% CI, 6.7 to 8.5). Among a random subgroup of 61 vaccinees who also received two doses but did not have a detectable protective response to the outbreak strain, 86.9% (95% CI, 75.8 to 94.2) were seropositive for the 44/76-SL strain, for which there was a geometric mean titer of 17.4 (95% CI, 13.0 to 23.2), whereas 100% of these vaccinees (95% CI, 94.1 to 100) were seropositive for the 5/99 strain and had a higher geometric mean titer (256.3; 95% CI, 187.3 to 350.7). The response to the outbreak strain was moderately correlated with the response to the 44/76-SL strain (Pearson's correlation, 0.64; P<0.001) but not with the response to the 5/99 strain (Pearson's correlation, -0.06; P = 0.43). CONCLUSIONS: Eight weeks after the second dose of the 4CMenB vaccine was administered, there was no evidence of an hSBA response against the outbreak strain in 33.9% of vaccinees, although no cases of meningococcal disease caused by N. meningitidis B were reported among vaccinated students.

AB - BACKGROUND: In December 2013, a multicomponent meningococcal serogroup B (4CMenB) vaccine was used before licensure on the basis of special consideration by the Food and Drug Administration to respond to an outbreak of Neisseria meningitidis B at a U.S. university. Data suggested that vaccination would control the outbreak because isolates expressed antigens that were closely related to the vaccine antigens (factor H-binding protein [fHbp] and neisserial heparin-binding antigen). We quantified the immune responses induced by 4CMenB during the outbreak. METHODS: We conducted a seroprevalence survey among students to assess vaccination status and collect serum specimens to quantify titers of serum bactericidal antibodies (SBA) with an assay that included human complement (hSBA). We compared the proportion of vaccinated and unvaccinated participants who were seropositive for the outbreak strain and for one closely related reference strain (44/76-SL, which included fHbp) and one mismatched reference strain (5/99, which included neisserial adhesin A), both of which were used in vaccine development. Seropositivity was defined as an hSBA titer of 4 or higher. RESULTS: Among the 499 participants who received two doses of the 4CMenB vaccine 10 weeks apart, 66.1% (95% confidence interval [CI], 61.8 to 70.3) were seropositive for the outbreak strain, although the geometric mean titer was low at 7.6 (95% CI, 6.7 to 8.5). Among a random subgroup of 61 vaccinees who also received two doses but did not have a detectable protective response to the outbreak strain, 86.9% (95% CI, 75.8 to 94.2) were seropositive for the 44/76-SL strain, for which there was a geometric mean titer of 17.4 (95% CI, 13.0 to 23.2), whereas 100% of these vaccinees (95% CI, 94.1 to 100) were seropositive for the 5/99 strain and had a higher geometric mean titer (256.3; 95% CI, 187.3 to 350.7). The response to the outbreak strain was moderately correlated with the response to the 44/76-SL strain (Pearson's correlation, 0.64; P<0.001) but not with the response to the 5/99 strain (Pearson's correlation, -0.06; P = 0.43). CONCLUSIONS: Eight weeks after the second dose of the 4CMenB vaccine was administered, there was no evidence of an hSBA response against the outbreak strain in 33.9% of vaccinees, although no cases of meningococcal disease caused by N. meningitidis B were reported among vaccinated students.

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