The purpose of this review is to summarize current knowledge on cell-mediated immunity (CMI) against vaccine-preventable diseases (VPD) included – and considered to be included – in the National Immunization Program (NIP) in Sweden and, to investigate the possible added value of CMI in vaccine surveillance and in research to address knowledge gaps.
The report provides primarily an information basis for future decision-making regarding the role of CMI in the surveillance of VPD, at the Agency. It may also be of value to professionals and specialists such as managers of NIPs and managers of laboratory surveillance of NIPs, as well as national and international communicable disease control and prevention authorities and public health agencies.
Purpose of this review
The purpose of this review is to summarize current knowledge on cell-mediated immunity (CMI) against vaccine-preventable diseases (VPD) included –and considered to be included - in the National Immunization Program (NIP) in Sweden and, to investigate the possible added value of CMI in vaccine surveillance and in research to address specific issues that might be useful in the future for design of optimized immunization schedules, timing of booster immunizations and evaluation of novel vaccine concepts and adjuvants targeted at eliciting CMI responses. CMI analysis are also discussed in a broader perspective, and as part of a strategic and long-term work with the development of the NIP. Also the applicability of CMI methods for large-scale surveillance of vaccine-induced immunity is addressed.
The report is based on a comprehensive scoping literature review on cell-mediated immunity including scientific peer-reviewed literature from the past 12 years, available grey literature, and ad-hoc search. A survey on CMI methods established at the Public Health Agency of Sweden and the Nordic countries was also performed.
Added value of analysis of CMI for vaccine surveillance?
Humoral immune responses have been established as the primary immunological correlate of protection against most VPD in the Swedish NIP, and protective antibody levels are defined for several of these. Vaccine-induced cell-mediated immunity (CMI) may also correlate to protection against certain diseases, where antibodies either do not provide protection such as tuberculosis or have waned to non-protective levels over time after vaccination. However, CMI analysis suffers from a lack of defined correlates of protection. Only a few studies have been able to propose protective levels of some CMI parameters (tuberculosis, influenza).
Large-scale analysis of CMI is costly and labor-intensive, and can thus not replace serological immune surveillance in the general population, which is currently performed by high throughput serological assays.
Added value of analysis of CMI for research and knowledge gaps?
Studies aiming at better understanding protective immunity in individuals or specific target populations are important.
Conventional CMI methods will remain essential in evaluation of vaccine-induced responses in the future. However, these approaches are generally limited to the analysis of a small number of components of the immune system and are not sufficient to assess the full complexity of structures and dynamics of the immune system as a whole. Recent advances in high throughput technologies and deeper understanding of the immune system have given rise to a new approach, the so-called systems immunology/vaccinology, with a holistic view of the immune system, where measurement of cell mediated immunity is only one of several arms to assess.
In conclusion, CMI has currently no role in routine surveillance of the VPDs in the NIP in Sweden. For knowledge gaps and research purposes it may be useful in different areas, as summarized in the sections CMI in protection for vaccine preventable diseases under Results. Selected examples of suggested use of CMI:
- Estimation of duration of protection of MMR vaccine induced immunity in the absence of epidemics
- In the development of new vaccines against tuberculosis
- To investigate the optimal timing of pertussis booster vaccination
- To measure long-term immunity against Hepatitis B and HPV after vaccination
In planning and carrying out research studies using cmi, several issues need to be considered, such as:
- Data from national serosurveillance studies on population-level immunity should be taken into account for decision on any future study based on CMI analysis
- Explore the possibility of collaboration with the Nordic and other European countries to create a collaborative CMI platform
- Jointly planned CMI studies to be carried out through collaboration with the Nordic and other European countries or other stakeholders
- Continuously surveil the scientific literature on new vaccines and CMI with specific focus on the development of national immunization programs.