Abstract
Human cytomegalovirus (HCMV) infects more than 70% of the human population worldwide. HCMV is responsible for high morbidity and mortality in immunocompromised patients and remains the leading viral cause of congenital birth defects. Despite considerable efforts in vaccine and therapeutic development, HCMV infection still represents an unmet clinical need and a life-threatening disease in immunocompromised individuals and newborns. Immune repertoire interrogation of HCMV seropositive patients allowed the identification of several potential antigens for vaccine design. However, recent HCMV vaccine clinical trials did not lead to a satisfactory outcome in term of efficacy. Therefore, combining antigens with orthogonal technologies to further increase the induction of neutralizing antibodies could improve the likelihood of a vaccine to reach protective efficacy in humans. Indeed, presentation of multiple copies of an antigen in a repetitive array is known to drive a more robust humoral immune response than its soluble counterpart. Virus-like particles (VLPs) and nanoparticles (NPs) are powerful platforms for multivalent antigen presentation. Several self-assembling proteins have been successfully used as scaffolds to present complex glycoprotein antigens on their surface. In this review, we describe some key aspects of the immune response to HCMV and discuss the scaffolds that were successfully used to increase vaccine efficacy against viruses with unmet medical need.
Highlights
Human cytomegalovirus (HCMV) is a ubiquitously distributed member of the Herpesviridae family belonging to the Betaherpesvirinae sub-family; it infects 70% of the human adult population worldwide [1,2] and primary infection is usually asymptomatic in immunocompetent individuals
The primary cellular response to HCMV infection arises from natural killer (NK) cells, which trigger the release of inflammatory cytokines and cause lysis or apoptosis of infected cells [24]
Variation Biotechnologies Incorporated (VBI) laboratories generated an Enveloped virus-like particles (eVLPs) vaccine expressing an HCMV glycoprotein B (gB) full-length or a chimeric gB protein, where the induce a neutralizing antibody response 10-fold higher compared to their soluble recombinant protein counterpart [90]
Summary
Human cytomegalovirus (HCMV) is a ubiquitously distributed member of the Herpesviridae family belonging to the Betaherpesvirinae sub-family; it infects 70% of the human adult population worldwide [1,2] and primary infection is usually asymptomatic in immunocompetent individuals. Infection or viral reactivation in immunodeficient individuals such as AIDS patients, solid organ (SOT) or hematopoietic stem cells (HSCT) transplant patients causes morbidity and mortality [4,5]. Viruses 2020, 12, 35 vaccine capable of preventing HCMV infection, congenital transmission and viral spreading after SOT or HSCT from seropositive donors to seronegative recipients [10]. The vaccine demonstrated only modest efficacy in preventing primary HCMV infections in seronegative women and in the reduction of viremia in transplant recipients [14,15]. A recent study demonstrated that seronegative patients vaccinated with the gB/MF59 vaccine developed a faster humoral response against gB after solid organ transplantation from seropositive donors [16]. We will summarize the current findings on the adaptive immune response to HCMV and provide an update on the new methodologies available to boost the immune response against infectious diseases using virus-like particles (VLPs) and nanoparticles (NPs)
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