Title: The immunological effects of co-administering diphtheria, tetanus, pertussis combined vaccine with measles vaccine to 9 month old Gambian infants

Authors: F. Noho-Konteh 1, J. Adetifa 1, M.T. Lee 1, F. Barker. 1, M. Cox 1, A. Drammeh 1, S. Nyamweya 1, B. Kampmann 1, M. van der Sande 2, F. van der Klis 2, S. Rowland-Jones 1, H. Whittle 1, T. Forster 3, P. Dickinson 3, P. Ghazal 3, K.L. Flanagan 1

Authors Affiliation: 1 MRC Laboratories, Fajara, The Gambia; 2 National Institute for Public Health & the Environment, Bilthoven, The Netherlands; 3 Division of Pathway Medicine, University of Edinburgh, Scotland, UK;

Introduction & Aims
Many commonly used vaccines were developed empirically, and there is surprisingly poor understanding of how they work. There is increasing evidence that aside from vaccine-specific effects, vaccines have non-specific effects (NSE) leading to altered morbidity and mortality from other infections. Broadly, live vaccines such as measles vaccine (MV) are beneficial, whereas inactivated vaccines such as diphtheria, tetanus, pertussis vaccine (DTP) may be deleterious. When live and inactivated vaccines are administered simultaneously the beneficial NSE of the live vaccine are lost. Females are generally more susceptible to these NSE than males. This study aimed to investigate the immunological mechanisms behind these observations.

Methods
303 children were randomised to one of three vaccine groups; Group 1: MV at 9 months; Group 2 DTP + MV at 9 months; Group 3 DTP at 9 months. Children were bled at 9 months and 4 weeks later. Females and males were randomized separately. Immunological assays included overnight whole blood cultures, flow cytometry for intracellular cytokines, b-2 microglobulin (b2M) ELISA, measles and DTP Ab assays, and whole human transcriptome microarray analysis from whole blood.

Results
Distinct male / female differences were found in b2M levels, cytokines in culture supernatants, and the transcriptome profile, with females generally being more immune activated and pro-inflammatory than males. Vaccine antibody levels were unaffected by combining the vaccines.

Conclusion
This study shows evidence of sex differences in response to vaccines, and that combining MV with DTP alters the immune profile.

This work was funded by MRC(UK)