Effect of Tdap upon antibody response to meningococcal polysaccharide when administered before, with or after the quadrivalent meningococcal TT-conjugate vaccine (coadministered with the 13-valent pneumococcal CRM197-conjugate vaccine) in adult Hajj pilgrims: A randomised controlled trial



Tashani M, Alfelali M, Barasheed O, Alqahtani AS, Heron L, Wong M, Rashid H, Findlow H, Borrow R, Booy R.


Vaccine. 2018 Jul 5;36(29):4375-4382. doi: 10.1016/j.vaccine.2018.04.033. Epub 2018 Jun 5.


Hajj pilgrims are susceptible to several serious infections and are required to
receive multiple vaccinations. Polysaccharide-protein conjugate vaccines contain
carrier proteins such as tetanus toxoid (TT), diphtheria toxoid or a mutant of
diphtheria toxoid (CRM197). These carrier proteins may interact with other conjugate
or combination vaccines containing tetanus or diphtheria on concurrent or sequential
administration. We examined the immune interaction of separate and concomitant
administration of a tetanus/diphtheria/acellular pertussis (Tdap) vaccine with a
TT-conjugated quadrivalent meningococcal vaccine (MCV4) (coadministered with
13-valent pneumococcal CRM197-conjugate vaccine [PCV13]) in adult Australian
pilgrims before attending Hajj in 2015. We randomly assigned each participant to one
of three vaccination schedules. Group 1 received Tdap 3-4 weeks before receiving
MCV4 coadministered with PCV13. Group 2 received all three vaccines concomitantly.
Group 3 received MCV4 and PCV13 3-4 weeks before Tdap. Blood samples were collected
at baseline, at each vaccination visit and 3-4 weeks after vaccination and tested
for response to meningococcal serogroups C, W and Y using a serum bactericidal
antibody (rSBA) assay with baby rabbit complement, and to diphtheria and tetanus
toxoid, measuring IgG antibodies by ELISA. Participants completed symptom diaries
after each vaccination. A total of 166 participants aged 18-64 (median 42) years
were recruited, of whom 160 completed the study. Compared to the other groups, Group
1 (given Tdap first) had significantly lower proportion of subjects achieving a
≥4-fold rise in rSBA for serogroup W. No difference was detected across the three
groups in achieving protection threshold (rSBA ≥8 post vaccination) or SBA geometric
mean titre (GMT) post vaccination. Group 3, which was given MCV4/PCV13 first, had
high levels of antibody against diphtheria and tetanus than the other groups, when
tested prior to receipt of Tdap; Only the anti-tetanus responses remained
significantly higher after Tdap administration. No serious adverse events were
reported. In conclusion, when multiple vaccination is required for Hajj pilgrims,
administering Tdap concurrently with MCV4/PCV13 produces adequate immune responses,
and avoids meningococcal immune interference, in the convenience of a single
consultation. However, giving Tdap 3-4 weeks after MCV4/PCV13 has the advantage of
an enhanced tetanus toxoid response. The trial is Trials Registry (ANZCTR):

Keywords: .

Link/DOI: 10.1016/j.vaccine.2018.04.033