Doctoral Defence in Biomedical Sciences – Poorya F. Pajoohian

On Monday, 14 September, Poorya F. Pajoohian will defend his doctoral thesis in biomedical sciences at the Faculty of Medicine, University of Iceland. The thesis is entitled:

Heterologous and homologous prime-boost immunization strategies to enhance immune responses in early life.

The opponents are Dr Annalisa Ciabattini, Associate Professor at the University of Siena, Italy, and Dr Sigurbjörg Þorsteinsdóttir, Professor Emerita at the Faculty of Medicine and Head of Department at the University of Iceland's Institute for Experimental Pathology at Keldur.

Ingileif Jónsdóttir, Professor Emerita at the Faculty of Medicine, was the principal supervisor, and Stefanía P. Bjarnarson, Associate Professor at the Faculty of Medicine, was the supervisor. In addition, Dennis Christensen, Head of Research and Development of Immunoenhancers at Croda Pharma, Copenhagen, and Þórunn Ásta Ólafsdóttir, Associate Professor at the Faculty of Medicine, served on the doctoral committee.

Ingibjörg Harðardóttir, Professor, will chair the ceremony, which will take place in Hátíðasalur in the main building of the University of Iceland and begin at 9:00 a.m.

Abstract

In early life the immune system is characterized by generation of weaker and less durable vaccine-induced antibody responses than in adulthood. The overall aim of this thesis project was to determine how heterologous prime-boost immunization routes in comparison with the conventional parenteral homologous immunization shape early life humoral immunity to a pneumococcal conjugate vaccine, Pn1-CRM197, and to develop immunization strategies capable of improving both systemic and mucosal responses in early life.

A neonatal mouse model was used in the study. Mice were immunized with Pn1-CRM197 formulated with the adjuvants CAF01 or mmCT for subcutaneous or intranasal administration, respectively. Vaccine-specific IgG and IgA antibody responses, germinal center activity, memory B cell generation, plasmablast/plasma cell differentiation and their expression of the survival and activation receptors BAFF-R, TACI and BCMA were examined.

Immunization schedules that included a mucosal administration enhanced vaccine-specific IgA responses compared with homologous subcutaneous immunization. Homologous subcutaneous/subcutaneous immunization preferentially induced germinal center responses in spleen and inguinal lymph nodes, promoted plasmablast/plasma cell differentiation and yielded high systemic IgG responses. In contrast, heterologous subcutaneous/intranasal immunization favoured the generation of IgM⁺ germinal center-derived memory B cells and stronger IgA responses.
Reversal of the heterologous immunization schedule, consisting of intranasal priming and subcutaneous booster, preserved the mucosal advantage of intranasal immunization while inducing systemic IgG responses comparable to homologous subcutaneous/subcutaneous immunization, alongside enhanced serum and salivary IgA responses, increased bone marrow homing of BCMA⁺ plasmablasts/plasma cells and expanded memory B cell output. Together, these studies demonstrate that in early life, the route and order of prime-boost immunization affect the magnitude, localization and quality of humoral immunity. Among the immunization strategies tested, intranasal priming followed by subcutaneous booster emerged as the most suitable approach.

Keywords: neonatal immunization; pneumococcal conjugate vaccine; heterologous and homologous prime-boost; mucosal immunity; germinal center responses.

About the Doctoral Candidate

Poorya Foroutan Pajoohian was born in 1993 in Kurdistan. He received a B.Sc. degree in biomedical sciences from Kurdistan University of Medical Sciences in Kurdistan, Iran, in 2016, and a Master's degree in clinical immunology from Kurdistan University of Medical Sciences in Kurdistan, Iran, in 2019. He began his doctoral studies at the Faculty of Medicine, University of Iceland, in 2021.

Poorya's mother is Farasat Bakhtiary, and his father is Salah Foroutan Pajoohian. He has a son, Kardo, and his fiancée is Sif Baldursdóttir Isaksen. Poorya works as a scientist in the Quality Control Department at Alvotech.