Oral Spray Immunization May Be an Alternative to Intranasal Vaccine Delivery to Induce Systemic Antibodies but not Nasal Mucosal or Cellular Immunity

Abstract

Sixty-five healthy adult volunteers were immunized four times at 1-week intervals with an inactivated whole-virus influenza vaccine based on the strain A/New Caledonia/20/99 (H1N1) without adjuvant. The vaccine was administered as nasal spray with a newly developed device to secure intranasal delivery (OptiMist TM , OptiNose AS, Oslo, Norway), as regular nasal spray, nasal drops or as an oral spray. Significant IgA-antibody responses in nasal secretions were induced in volunteers immunized intranasally but not after oral spray immunization. In saliva, IgA antibodies were only marginally amplified even after oral spray immunizations. At least 73% of the volunteers belonging to any group of vaccine delivery reached serum haemagglutination inhibition titres of 40 or higher, considered protective against influenza, after only two vaccine doses. Those who had the vaccine delivered intranasally also showed evidence from in vitro secretion of granzyme B that cytotoxic T cells had been stimulated. Although immunization with the breath-actuated OptiMist TM device and nasal drops were superior with respect to both mucosal and systemic immune responses, oral spray immunization might still be considered for studies of mucosal adjuvants that are not yet acceptable for intranasal use.

Nasal drug delivery devices: characteristics and performance in a clinical perspective—a review

“…This is often used in animal studies where the animals are anesthetized or sedated, but can also be done in humans even without local anesthetics if care is taken to minimize contact with the sensitive mucosal membranes [50]. This method is, however, not suitable for self-administration.…”

“…In contrast to the self-administration with the OptiNose device, the nasal drops were delivered by an assistant inserting the pipette tip in a controlled manner beyond the nasal valve with the neck extended. These results suggest that Bi-Directional™ devices are a practical delivery method capable of producing a clinically relevant broader and deeper distribution of vaccines to the nasal respiratory mucosa, areas rich in dendritic cells and aggregates of lymphoid tissue, offering potential for a range of vaccines to produce improved immune response in non-parenteral delivery forms [24, 50]. …”

“…Influenza vaccine: In a four-armed parallel group study with a whole-virus influenza liquid vaccine without adjuvant, delivery with the breath-powered Bi-Directional™ OptiNose device and nasal drops were found to provide better overall immune response than a traditional nasal spray and an oral spray [50]. In contrast to the self-administration with the OptiNose device, the nasal drops were delivered by an assistant inserting the pipette tip in a controlled manner beyond the nasal valve with the neck extended.…”

Pharmaceutical Aspects of Intranasal Delivery of Vaccines Using Particulate Systems

“…A novel nasal spray device (Optinose BD device) has been recently developed and is claimed to address most of the challenges of nasal vaccine delivery 231, 234, 235. This bidirectional nasal delivery device is a newer concept that takes advantage of the posterior connection between the nasal passages which persists when the soft palate automatically closes during oral exhalation.…”

Dried influenza vaccines: Over the counter vaccines

“…Furthermore, nasal delivery devices like, Lyphodose ® and OptiNose ® have been developed to deliver the exact amounts of powders in the nasal cavity. 22,23 Dermal administration of dried influenza vaccines have been tested in clinical and preclinical studies via two methods, jet injectors and micro-needles respectively. Clinical Phase1 studies have shown the successful use of the powderject been used for stabilization i.e., trehalose and inulin.…”