Robust antigen-specific humoral immune responses to sublingually delivered adenoviral vectors encoding HIV-1 Env: Association with mucoadhesion and efficient penetration of the sublingual barrier

Abstract

The efficient induction of virus-specific mucosal antibodies is an important unmet objective in Human Immunodeficiency Virus Type-1 (HIV-1) vaccine research. One promising approach is sublingual (SL) immunization. We examined the effectiveness of SL delivery of two different viral vectors: (i) a recombinant adenovirus (rAd5), and (ii) a Herpes Simplex Virus Type-1 amplicon vector (HSV-1). Initial in vitro videomicroscopy experiments showed that rAd5 particles were trapped in saliva (i.e., that Ad5 was mucoadhesive) - unlike HSV-1 virions, which migrated freely in both saliva and water. In vivo imaging studies in mice revealed that only the rAd5 vector efficiently transduced the SL epithelium. Consistent with this, SL delivery of an rAd5 encoding HIV-1 envelope glycoprotein (Env) resulted in robust antigen-specific antibody responses in plasma and in vaginal washes, whereas SL delivery of a HSV-1 amplicon vector encoding HIV-1 Env failed to elicit Env-specific antibodies. In contrast, both vectors elicited equivalent humoral responses following intramuscular (IM) delivery. Finally, SL delivery of the rAd5:Env vector resulted in elevated levels of Env-specific serum IgA, and vaginal IgA and IgG, when compared to IM delivery of the same vector. These results findings shed light on vector properties (mucoadhesion, penetration of the sublingual barrier) which may be important for the induction of potent humoral immune responses following sublingual vector administration. Our data also show that SL delivery of an Env-encoding rAd5 vector can elicit a potent antigen-specific mucosal antibody response in the absence of adjuvant. Overall, these findings support the further exploration of the SL delivery route for HIV-1 vaccine delivery.

Evaluation of recombinant adenovirus vaccines based on glycoprotein D and truncated UL25 against herpes simplex virus type 2 in mice

“…Antibodies can protect humans against central nervous system infection , and recombinant adenoviruses have been shown to elicit robust antigen‐specific serum IgG antibody responses to transgenes . In our study, we developed recombinant replication‐defective adenoviruses to deliver gD2 alone, ΔUL25 alone or the gD2ΔUL25 fusion protein for comparison with FI‐HSV2 in terms of immunogenicity and protective efficacy against HSV‐2 challenge.…”

Buccal and sublingual vaccine delivery

“…Sublingual immunization with rAdV encoding the conserved influenza nucleoprotein antigen [28] or the soluble globular head of hemagglutinin [29] protected mice against influenza virus infection. Furthermore, sublingual administration of rAd5 vectors encoding HIV proteins induced both significant antigen-specific humoral (serum and mucosal IgG and IgA) [30] and cellular (systemic and mucosal CTL responses) [31] immune responses. Moreover, sublingual vaccination with rAdV encoding a truncated S protein (rAdV-S), which is a major antigenic protein present on severe acute respiratory syndrome-associated coronavirus (SARS-CoV), induced systemic neutralizing antibodies and airway IgA antibody responses in mice.…”

Intra-cheek immunization as a novel vaccination route for therapeutic vaccines of head and neck squamous cell carcinomas using plasmo virus-like particles

“…Sublingual immunotherapy has been widely used for therapeutic allergy vaccines. 25 Although several studies have showed the efficiency of the sublingual route to induce tolerance, others have observed cell-mediated immune responses against pathogens, [26][27][28][29] or tumors. 30 Similarly, Sandoval et al have reported that the IN route was able to induce good antitumoral responses in a model of oral cancer and lung.…”