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Immunogenicity of Quadrivalent Meningococcal Vaccine in HIV-infected Youth
George Siberry*1, J Lujan-Zilberman2, P Williams3, M Warshaw3, M Decker4, B Heckman5, E Demske6, J Read1, P Jean-Philippe7, S Nachman8, and IMPAACT Network P1065 Protocol Team
1Natl Inst of Child Hlth and Human Devt, NIH, Bethesda, MD, US; 2Univ of South Florida Coll of Med, Tampa, US; 3Harvard Sch of Publ Hlth, Boston, MA, US; 4Sanofi Pasteur Inc, Swiftwater, PA, US; 5Frontier Sci & Tech Res Fndn, Amherst, NY, US; 6Social & Sci Systems Inc, Silver Spring, MD, US; 7Henry M Jackson Fndn, Div of AIDS, NIAID, NIH, Bethesda, MD, US; and 8State Univ of New York at Stony Brook, US
Background: Quadrivalent meningococcal vaccine (MCV4)
is routinely recommended for adolescents in the United States. Healthy youth
respond to MCV4 at high rates (80 to 97%), varying by meningococcal serogroup.
There are no data regarding the immunogenicity of MCV4 in HIV-infected youth.
Methods: P1065 is a phase I/II safety and
immunogenicity trial of MCV4 in HIV-infected youth (11 to 24 years old)
performed at 27 clinical sites of the IMPAACT network in the United States. All subjects received 1 dose of MCV4 at entry; at 24 weeks, subjects in group1
(CD4 ≥15%) were randomized to receive a second dose vs no dose of MCV4,
while all eligible subjects in group 2 (CD4 <15%) received a second dose. Immunogenicity
after the first MCV4 dose was evaluated as the proportion of subjects with a ≥4-fold
rise in serum bactericidal antibody against each meningococcal serogroup (A, C,
Y, and W-135) at 28 days after immunization. Multivariable logistic regression analysis
was used to assess the association of age, CD4 percentage, gender, CDC illness
class, and viral load on immunogenic response to serogroup C.
Results: Of 318 eligible enrolled subjects who
received at least 1 dose of MCV4, 297 had serology results. Enrollment was
stratified by CD4 percentage: CD4 <15% (n = 34, 11%), CD4 = 15 to 24% (n = 119,
40%), and CD4 ≥25% (n = 144, 48%). The median age was 18 years; 59% were
male, 51% were black, and 49% had a viral load ≤400 copies/mL at entry.
The proportion with ≥4-fold serum bactericidal antibody titer rise to serogroup
A, C, Y, and W-135 were 69±3%, 53±3%, 63±3%, and 73±3%, respectively. Of the
total, 88% had ≥4-fold serum bactericidal antibody titer rise to at least
1 serogroup. When excluding the subjects with baseline immunity (serum
bactericidal antibody titer ≥1:128) to each serogroup (A, 41%; C, 12%; Y,
35%; W-135, 15%), the proportions with ≥4-fold serum bactericidal
antibody titer rise to serogroup A, C, Y, and W-135 were 77±3%, 51±3%, 66±3%,
and 73±3%, respectively. In multivariable logistic regression analysis, lower entry
CD4 percentage stratum, viral load >10,000 copies/mL, CDC class C, and female
gender were associated with significantly lower odds of response to serogroup C.
Conclusions: Many HIV-infected youth naturally
acquire meningococcal immunity, especially to serogroup A and Y. MCV4 is
immunogenic in most HIV-infected youth, but response rates are lower than in
healthy youth. Higher CD4 (≥15%) and lower HIV viral load were associated
with greater immunogenicity.
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