A novel influenza subunit vaccine composed of liposome-encapsulated haemagglutinin/neuraminidase and IL-2 or GM-CSF. I. Vaccine characterization and efficacy studies in mice.

• Abstract: The aim of this study was to improve the potency of the currently used influenza subunit vaccines, which are of relatively low efficiency in high-risk groups. Influenza A virus (Shangdong/9/93) haemagglutinin/neuraminidase (H3N2), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) were encapsulated, each separately or combined, in multilamellar vesicles composed of dimyristoyl phosphatidylcholine. BALB/c mice were immunized once, i.p. or s.c., with 0.05-2.0 microg HN administered either as free antigen (F-HN), adsorbed to aluminum hydroxide (Al-HN), or encapsulated in liposomes (Lip-HN), separately or together with 1 x 10(2)-4.5 x 10(4) units of free or encapsulated cytokines. Serum antibodies were assayed on days 11-360 by the haemagglutination-inhibition (HI) test and ELISA. Protective immunity against intranasal virus challenge was determined at 9-14 months post-vaccination. The following results were obtained: (1) The efficiency of encapsulation in liposomes was 95, 90 and 38% for HN, IL-2 and GM-CSF, respectively, and the liposomal preparations were highly stable as an aqueous dispersion for > 2 months at 4 degrees C. (2) Following immunization with 0.5 microg Lip-HN, there was an earlier, up to 50-fold stronger, and 3-5 times longer response than that obtained with nonliposomal HN. (3) Coimmunization with free cytokines further increased the response 2-20 times and the two cytokines had an additive effect. (4) Liposomal cytokines were 2-20 times more effective than the free cytokines and their stimulatory effect was more durable. (5) A 100% seroconversion (HI titer > or = 40) was achieved with only 10-25% of the routinely used antigen dose, by encapsulating either antigen or cytokine. (6) The level of protection following vaccination with the combined liposomal vaccines was 70-100% versus 0-25% in mice immunized with Al-HN alone, and no toxicity was observed. In conclusion, our animal experiments show that the liposomal vaccines are superior to the currently used influenza vaccines, increasing the response by 2-3 orders of magnitude in mice. This approach may also prove valuable for subunit vaccines against other microorganisms.
• Authors: I Babai, S Samira, Y Barenholz, Z Zakay-Rones, E Kedar (Affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.)
• Journal: Vaccine (Vaccine) Vol. 17 Issue 9-10 Pg. 1223-38 (Mar 5 1999) ISSN: 0264-410X [Print] ENGLAND
• PMID: 10195636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hemagglutinin Glycoproteins, Influenza Virus
• Influenza Vaccines
• Interleukin-2
• Liposomes
• Aluminum Hydroxide
• Granulocyte-Macrophage Colony-Stimulating Factor
• Neuraminidase

Topics

• Aluminum Hydroxide
• Animals
• Antibody Formation
• Enzyme-Linked Immunosorbent Assay
• Granulocyte-Macrophage Colony-Stimulating Factor (administration & dosage, immunology)
• Hemagglutinin Glycoproteins, Influenza Virus (administration & dosage, immunology)
• Influenza A virus (immunology)
• Influenza Vaccines (administration & dosage, chemistry, immunology)
• Interleukin-2 (administration & dosage, immunology)
• Liposomes
• Mice
• Mice, Inbred BALB C
• Neuraminidase (administration & dosage, immunology)
• Orthomyxoviridae Infections (prevention & control)