Promising Cytomegalovirus-Based Vaccine Vector Induces Robust CD8+ T-Cell Response

Abstract

Vaccination has had great success in combating diseases, especially infectious diseases. However, traditional vaccination strategies are ineffective for several life-threatening diseases, including acquired immunodeficiency syndrome (AIDS), tuberculosis, malaria, and cancer. Viral vaccine vectors represent a promising strategy because they can efficiently deliver foreign genes and enhance antigen presentation in vivo. However, several limitations, including pre-existing immunity and packaging capacity, block the application of viral vectors. Cytomegalovirus (CMV) has been demonstrated as a new type of viral vector with additional advantages. CMV could systematically elicit and maintain high frequencies of effector memory T cells through the “memory inflation” mechanism. Studies have shown that CMV can be genetically modified to induce distinct patterns of CD8+ T-cell responses, while some unconventional CD8+ T-cell responses are rarely induced through conventional vaccine strategies. CMV has been used as a vaccine vector to deliver many disease-specific antigens, and the efficacy of these vaccines was tested in different animal models. Promising results demonstrated that the robust and unconventional T-cell responses elicited by the CMV-based vaccine vector are essential to control these diseases. These accumulated data and evidence strongly suggest that a CMV-based vaccine vector represents a promising approach to develop novel prophylactic and therapeutic vaccines against some epidemic pathogens and tumors.

Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions

“…Special attributes of CMV vectored vaccines include the ability to maintain persistent immune stimulation and not being prone to attenuation by pre-existing immune responses. Also, CMV vector-induced HLA-E restricted CD8 + T cell responses have the potential to provide vaccine efficacy in all individuals regardless of MHC-class I genotypes (173,174).…”

Preclinical Progress of Subunit and Live Attenuated Mycobacterium tuberculosis Vaccines: A Review following the First in Human Efficacy Trial

“…This study provides evidence that a long-acting vaccine could control M. tb at early stages of infection. It is important to note that there is a major concern of safety regarding CMV-based vaccines and whether an attenuated virus can maintain its ability to elicit robust immunity is still to be determined [108].…”

Application of antigenic biomarkers for Mycobacterium tuberculosis

“…CMV vectors can be genetically altered to stimulate highly diverse CD8 + T-cell responses that differ in their intended epitope, making it possible to uniquely tailor the CD8 + T-cell response for each disease to maximize therapeutic or prophylactic protection. This vaccine has shown protection in preclinical studies, with sustained antigenic expression representing long-term immunity, an attractive strategy for a new TB vaccine (Früh and Picker, 2017;Liu et al, 2019). Another strategy is the use of messenger RNA (mRNA) as a vaccine vector.…”