Published on 15 September 2025

Blog Kirill Lotonin – African swine fever

“A comprehensive analysis of both protective and detrimental immune responses to ASFV is essential for the development of a safe and effective vaccine. ”

From complexity to clarity: exploring immunity to African swine fever virus to advance vaccine development

African swine fever virus (ASFV) causes a severe hemorrhagic disease in domestic pigs and wild boars. This poses a significant threat to the health and welfare of animals, as well as to the economy, in affected regions. ASFV has a complex, multilayered virion with only partially characterized antigens and employs various strategies to modulate the host's immune response. Together with limited knowledge of the mechanisms underlying immune protection, these factors hinder the development of safe and effective vaccines.

Interview with Dr. Kirill Lotonin

• What was the aim of your dissertation?

  The focus of my thesis was on characterizing adaptive immune responses following ASFV infection, and it consists of two parts. The first aim was to establish a framework for assessing the efficacy of live attenuated vaccine (LAV) candidates against African swine fever virus (ASFV) by correlating various immunological parameters with the clinical outcomes of the challenge infection in immunized pigs. The second aim was to characterize the diversity of viral B-cell antigens with the goal of developing a safer subunit vaccine against ASFV.

• What are the main findings of your dissertation?

  To achieve the first aim, we used a previously established model comparing specific pathogen-free (SPF) pigs with farm pigs, which differ in baseline immunological status, hygienic conditions, and resilience to the virus. Both groups were immunized with the attenuated Estonia 2014 ASFV strain and, after viral clearance, challenged with the highly virulent Armenia 2008 strain. Throughout this long-term experiment, the animals were monitored for innate and adaptive immune responses to identify correlates of protection (CoPs). These included an early and sustained interferon alpha (IFN-α) response, activation of antigen presentation pathways, controlled IL-8 levels during immunization, and a strong induction of memory T helper and cytotoxic T cells following the challenge.
  
  In the second project, we collaborated with a biotech company that developed a proteome-scale microarray to screen for antibodies in immune sera that bind to ASFV proteins. This approach allowed us to identify novel B-cell antigens, some of which were used to generate virus-like particle vaccine candidates. They were shown to be immunogenic in both mice and pigs, however, the antibody response against the antigens was not sufficient to confer protection against the virulent ASFV strain.

  

  Model of protective immune responses against ASFV challenge in immunized pigs. — © Created in BioRender. Lotonin, K.

• To what extent will your findings help to advance research?

  Currently, LAVs represent the most promising strategy to combat ASF, with their administration shown to provide 100% protection in many studies. Nevertheless, their widespread application is not yet possible due to safety concerns, such as the risk of reversion to virulence and potential complications in immunocompromised hosts, as well as the limited understanding of the mechanisms underlying protection and pathogenesis following vaccination. The identified CoPs will enable a more rational vaccine design and facilitate the evaluation of new vaccine candidates. In parallel, we contributed to an ongoing effort to develop a subunit ASFV vaccine with an improved safety profile. The identified antigens can be further tested using alternative delivery systems that ideally induce both humoral and cellular immune responses.

• What aspect of this work are you especially proud of?

  When I started working at IVI in 2020, ASFV was not a hot topic, since SARS‑CoV‑2 was taking over global attention at that time. Now, it’s incredible for me to see how ASFV research has evolved in Europe and worldwide over the past five years, and I feel both proud and lucky to have been part of its growth. I really believe that the data generated at the institute has a significant impact. In addition, working at IVI has shaped me both personally and professionally, and taught me many skills for approaching various scientific questions.

• What did you especially like about your dissertation?

  ASFV research at IVI is truly a collaborative effort, bringing together experts in systems and molecular immunology, virology, and veterinary science. While always having guidance and support, I really appreciated the high degree of trust and freedom I was given in my project.

• How was your time at the IVI?

  Although the containment space is limited and one can feel isolated from the outside world, there is a high chance to meet great people in the lab. I formed strong connections with colleagues, and these relationships really helped me get through the challenges of my PhD.

• What are your plans now, what are you going to do next?

  I recently submitted my thesis and enjoyed the summer in Bern as compensation for all the time I spent writing, soaking up the sun. I’m also looking for my next research position in Europe, where I aim to study the immune response to a new group of pathogens.

Link to the publication (eLife):
Correlates of protection against African swine fever virus identified by a systems immunology approach

Authors
Kirill Lotonin, Francisco Brito, Kemal Mehinagic, Obdulio García-Nicolás, Matthias Liniger, Noelle Donzé, Sylvie Python, Stephanie Talker,Tosca Ploegaert, Nicolas Ruggli, Charaf Benarafa, Artur Summerfield

Information about African Swine Fever
What SPF and farm pigs teach us about protective immunity against African swine fever
African swine fever: Complex virus leaves many questions unanswered