Intranasal vaccine: Factors to consider in research and development

Xu, Haiyue; Cai, Lucy; Hufnagel, Stephanie; Cui, Zhengrong

doi:10.1016/j.ijpharm.2021.121180

Cited by 63 publications

(68 citation statements)

References 279 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Dv(10), Dv(50), Dv(90) values were 8.50 ± 1.6 µm, 92.3 ± 19.7 µm, and 283.5 ± 40.6 µm, respectively. Therefore, this powder formulation should have adequate aerosol performance properties for intranasal delivery as most of the particles were above 10 µm (Tiozzo Fasiolo et al, 2018; Xu et al, 2021, 2020).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Accelerated mass transfer from frozen thin films during thin-film freeze-drying

Wang

Kuang

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Freeze-drying, or lyophilization, is widely used to produce pharmaceutical solids from temperature-sensitive materials but the process is time and energy inefficient. Herein, using E. coli as a model live organism, whose viability in dry powders is highly sensitive to the water content in the powders, we demonstrated that the drying rate of thin-film freeze-drying (TFFD) is significantly higher than that of the conventional shelf freeze-drying, likely because the large total surface area from the loosely stacked frozen thin films and the low thickness of the thin films enable faster and more efficient mass transfer during freeze-drying. The highly porous nature and high specific surface area of the thin-film freeze-dried powders may have contributed to the faster mass transfer as well. Moreover, we demonstrated that TFFD can be applied to produce dry powders of E. coli and L. acidophilus with minimum bacterial viability loss (i.e., within one log reduction), and the L. acidophilus dry powder is suitable for intranasal delivery. It is concluded that TFFD technology is promising in addressing the time- and cost-inefficient issue of conventional shelf freeze-drying.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Therefore, this powder formulation should have adequate aerosol performance properties for intranasal delivery as most of the particles were above 10 µm (Tiozzo Fasiolo et al, 2018;Xu et al, 2021Xu et al, , 2020.…”

Section: Dry Powder Of L Acidophilus Prepared By Tffdmentioning

confidence: 99%

Accelerated mass transfer from frozen thin films during thin-film freeze-drying

Wang

Kuang

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nevertheless, the major challenges in the development of nasal vaccines are the delivery of antigen to APC in the respiratory tract and the safety issue. Approaches to overcome these obstacles include the use of a safe and effective adjuvant and delivery system to increase the efficacy and prolong the time of antigen uptake in the respiratory tract [255][256][257][258]. In this regard, TLR agonist-based nasal adjuvants are continuously being developed.…”

Section: Discussionmentioning

confidence: 99%

Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

Yang

Tseng

et al. 2022

Pharmaceutics

View full text Add to dashboard Cite

Vaccines are powerful tools for controlling microbial infections and preventing epidemic diseases. Efficient inactive, subunit, or viral-like particle vaccines usually rely on a safe and potent adjuvant to boost the immune response to the antigen. After a slow start, over the last decade there has been increased developments on adjuvants for human vaccines. The development of adjuvants has paralleled our increased understanding of the molecular mechanisms for the pattern recognition receptor (PRR)-mediated activation of immune responses. Toll-like receptors (TLRs) are a group of PRRs that recognize microbial pathogens to initiate a host’s response to infection. Activation of TLRs triggers potent and immediate innate immune responses, which leads to subsequent adaptive immune responses. Therefore, these TLRs are ideal targets for the development of effective adjuvants. To date, TLR agonists such as monophosphoryl lipid A (MPL) and CpG-1018 have been formulated in licensed vaccines for their adjuvant activity, and other TLR agonists are being developed for this purpose. The COVID-19 pandemic has also accelerated clinical research of vaccines containing TLR agonist-based adjuvants. In this paper, we reviewed the agonists for TLR activation and the molecular mechanisms associated with the adjuvants’ effects on TLR activation, emphasizing recent advances in the development of TLR agonist-based vaccine adjuvants for infectious diseases.

show abstract

“…Effective mucosal vaccines have the potential to limit mucosal infection and inhibit pathogen transmission, representing an approach to deal with emerging and re-emerging viruses ( 14 , 15 , 89 ). Most licensed mucosal vaccines are currently based on live-attenuated whole-microorganisms, as those are the most immunogenic formulations to prevent infectious diseases ( 18 , 90 – 93 ). Nevertheless, antigenically variable and highly transmissible pathogens such as PRRSV-2 and SARS-CoV-2 are not entirely suitable to be targeted by these immunogens, as a reversion to virulence may occur ( 94 , 95 ).…”

Section: Discussionmentioning

confidence: 99%

Combined Subcutaneous-Intranasal Immunization With Epitope-Based Antigens Elicits Binding and Neutralizing Antibody Responses in Serum and Mucosae Against PRRSV-2 and SARS-CoV-2

et al. 2022

View full text Add to dashboard Cite

New vaccine design approaches, platforms, and immunization strategies might foster antiviral mucosal effector and memory responses to reduce asymptomatic infection and transmission in vaccinated individuals. Here, we investigated a combined parenteral and mucosal immunization scheme to induce local and serum antibody responses, employing the epitope-based antigens 3BT and NG19m. These antigens target the important emerging and re-emerging viruses PRRSV-2 and SARS-CoV-2, respectively. We assessed two versions of the 3BT protein, which contains conserved epitopes from the GP5 envelope protein of PRRSV-2: soluble and expressed by the recombinant baculovirus BacDual-3BT. On the other hand, NG19m, comprising the receptor-binding motif of the S protein of SARS-CoV-2, was evaluated as a soluble recombinant protein only. Vietnamese mini-pigs were immunized employing different inoculation routes: subcutaneous, intranasal, or a combination of both (s.c.-i.n.). Animals produced antigen-binding and neut1ralizing antibodies in serum and mucosal fluids, with varying patterns of concentration and activity, depending on the antigen and the immunization schedule. Soluble 3BT was a potent immunogen to elicit binding and neutralizing antibodies in serum, nasal mucus, and vaginal swabs. The vectored immunogen BacDual-3BT induced binding antibodies in serum and mucosae, but PRRSV-2 neutralizing activity was found in nasal mucus exclusively when administered intranasally. NG19m promoted serum and mucosal binding antibodies, which showed differing neutralizing activity. Only serum samples from subcutaneously immunized animals inhibited RBD-ACE2 interaction, while mini-pigs inoculated intranasally or via the combined s.c.-i.n. scheme produced subtle neutralizing humoral responses in the upper and lower respiratory mucosae. Our results show that intranasal immunization, alone or combined with subcutaneous delivery of epitope-based antigens, generates local and systemic binding and neutralizing antibodies. Further investigation is needed to evaluate the capability of the induced responses to prevent infection and reduce transmission.

show abstract

Intranasal vaccine: Factors to consider in research and development

Cited by 63 publications

References 279 publications

Accelerated mass transfer from frozen thin films during thin-film freeze-drying

Accelerated mass transfer from frozen thin films during thin-film freeze-drying

Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

Combined Subcutaneous-Intranasal Immunization With Epitope-Based Antigens Elicits Binding and Neutralizing Antibody Responses in Serum and Mucosae Against PRRSV-2 and SARS-CoV-2

Contact Info

Product

Resources

About