Genetic immunization in the lung induces potent local and systemic immune responses

Abstract

The authors note the following: "Due to an error in the evaluation of the raw ITC-data, we reported the wrong sign for the enthalpy values and correspondingly incorrect entropy values. The correct values are as follows: at pH 5.7: ΔH −54 ± 4 kJ/ mol, ΔS −68 ± 14 J/mol K and at pH 7.2: ΔH −62 ± 6 kJ/mol and ΔS −98 ± 18 J/mol K (Table 3)." The authors note that on page 5381, left column, first paragraph, line 9 "Two E1 entities dimerize upon their interaction with heparin, requiring 8-12 sugar rings to form the heparin-bridged APP-E1 dimer in an endothermic and pH-dependent process that is characterized by a low micromolar dissociation constant" should have read "Two E1 entities dimerize upon their interaction with heparin, requiring 8-12 sugar rings to form the heparin-bridged APP-E1 dimer in an exothermic and pH-dependent process that is characterized by a low micromolar dissociation constant." On page 5384, right column, third paragraph, line 23 "This reaction is driven by high entropy contributions of around 300 J/mol · K, probably resulting from the release of associated ions and water molecules upon heparin binding, as also observed for other heparin-binding proteins (reviewed, e.g., in ref. 39)" should have read "This reaction is driven by significant enthalpic contributions, probably arising from protein-protein interactions, also observed for other heparin-binding proteins (reviewed, e.g., in ref. 39)." This error does not affect the conclusions of the article.

Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates

“…In addition, it is still unclear as to whether preexisting immunity due to natural adenovirus infections reduces the immunogenicity of the tonsillar adenoviral vector booster immunizations. However, delivery of adenoviral vectors by small aerosols to the lungs of rhesus macaques resulted in potent immune responses even in animals with preexisting adenoviral vector immunity (31,35,51), suggesting that such vector immunity can be overcome by mucosal delivery of adenoviral vectors. In addition, several adenovirus vectors have been developed based on chimpanzee or gorilla adenoviruses, which combine efficacy with evasion of preexisting vector specific neutralizing antibody responses (52,53).…”

Long-Term Antibody and Immune Memory Response Induced by Pulmonary Delivery of the Influenza Iscomatrix Vaccine

“…In recent years, a number of studies have explored the potential of lung vaccine delivery (9,10,13). The delivery of an influenza vaccine via the lungs, by exposing the recipient to the vaccine at the site of infection and thereby inducing a mucosal response, has the potential to increase the efficacy of protective immunity against this important pathogen.…”

“…Mucosal delivery has considerable potential for improving the effectiveness of vaccination against mucosal pathogens, by increasing immunity at the sites of infection. A number of studies have been carried out to investigate the potential of utilizing the lungs for the induction of protective immune responses, with encouraging results (9,10,13).…”

Pseudotyped Influenza A Virus as a Vaccine for the Induction of Heterotypic Immunity

“…S-FLU is based on inactivation of the vRNA encoding HA so does not contain a viable HA vRNA that could reassort with seasonal strains. Finally, given the complete control over replication, administration by small-droplet aerosol to the lung might be a viable and efficient way to immunize (7,49).…”

“…In general, in experimental settings without adjuvants, heterotypic immunity is efficiently induced by infections of the lung with live influenza A virus (28,38). Likewise, recombinant vectors capable of expressing the conserved viral proteins in host cells, particularly in the lung, tend to be efficient inducers of heterotypic protection (42,49). The specificity of the protective effect correlates with the conserved viral core antigens recognized by T cells (reviewed in references 12, 14, 20, 29, and 68), and protection can be transferred with core protein-specific T cells, particularly class I restricted cytotoxic T lymphocytes (32,59,70).…”