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Validation of Multi-epitope Peptides Encapsulated in PLGA Nanoparticles Against Influenza A Virus

Heng WT, Lim HX, Tan KO, Poh CL

Pharm Res, 2023 Aug;40(8):1999-2025.
PMID: 37344603 DOI: 10.1007/s11095-023-03540-x

BACKGROUND: Influenza is a highly contagious respiratory disease which poses a serious threat to public health globally, causing severe diseases in 3-5 million humans and resulting in 650,000 deaths annually. The current licensed seasonal influenza vaccines lacked cross-reactivity against novel emerging influenza strains as they conferred limited neutralising capabilities. To address the issue, we designed a multi-epitope peptide-based vaccine delivered by the self-adjuvanting PLGA nanoparticles against influenza infections.
METHODS: A total of six conserved peptides representing B- and T-cell epitopes of Influenza A were identified and they were formulated in either incomplete Freund's adjuvant containing CpG ODN 1826 or being encapsulated in PLGA nanoparticles for the evaluation of immunogenicity in BALB/c mice.
RESULTS: The self-adjuvanting PLGA nanoparticles encapsulating the six conserved peptides were capable of eliciting the highest levels of IgG and IFN- γ producing cells. In addition, the immunogenicity of the six peptides encapsulated in PLGA nanoparticles showed greater humoral and cellular mediated immune responses elicited by the mixture of six naked peptides formulated in incomplete Freund's adjuvant containing CpG ODN 1826 in the immunized mice. Peptide 3 from the mixture of six peptides was found to exert necrotic effect on CD3+ T-cells and this finding indicated that peptide 3 should be removed from the nanovaccine formulation.
CONCLUSION: The study demonstrated the self-adjuvanting properties of the PLGA nanoparticles as a delivery system without the need for incorporation of toxic and costly conventional adjuvants in multi-epitope peptide-based vaccines.

Matched MeSH terms: Adjuvants, Immunologic/chemistry
Fulltext Nanoparticles in influenza subunit vaccine development: Immunogenicity enhancement

Khalaj-Hedayati A, Chua CLL, Smooker P, Lee KW

Influenza Other Respir Viruses, 2020 Jan;14(1):92-101.
PMID: 31774251 DOI: 10.1111/irv.12697

The threat of novel influenza infections has sparked research efforts to develop subunit vaccines that can induce a more broadly protective immunity by targeting selected regions of the virus. In general, subunit vaccines are safer but may be less immunogenic than whole cell inactivated or live attenuated vaccines. Hence, novel adjuvants that boost immunogenicity are increasingly needed as we move toward the era of modern vaccines. In addition, targeting, delivery, and display of the selected antigens on the surface of professional antigen-presenting cells are also important in vaccine design and development. The use of nanosized particles can be one of the strategies to enhance immunogenicity as they can be efficiently recognized by antigen-presenting cells. They can act as both immunopotentiators and delivery system for the selected antigens. This review will discuss on the applications, advantages, limitations, and types of nanoparticles (NPs) used in the preparation of influenza subunit vaccine candidates to enhance humoral and cellular immune responses.

Matched MeSH terms: Adjuvants, Immunologic/chemistry
Self-adjuvanting vaccine against group A streptococcus: application of fibrillized peptide and immunostimulatory lipid as adjuvant

Azmi F, Ahmad Fuaad AA, Giddam AK, Batzloff MR, Good MF, Skwarczynski M, et al.

Bioorg Med Chem, 2014 Nov 15;22(22):6401-8.
PMID: 25438764 DOI: 10.1016/j.bmc.2014.09.042

Peptides are of great interest to be used as vaccine antigens due to their safety, ease of manufacturing and specificity in generating immune response. There have been massive discoveries of peptide antigens over the past decade. However, peptides alone are poorly immunogenic, which demand co-administration with strong adjuvant to enhance their immunogenicity. Recently, fibril-forming peptides such as Q11 and lipoamino acid-based carrier have been identified to induce substantial immune responses when covalently linked to peptide epitope. In this study, we have incorporated either Q11 or lipoamino acids to a peptide epitope (J14) derived from M protein of group A streptococcus to develop self-adjuvanting vaccines. J14, Q11 and lipoamino acids were also conjugated together in a single vaccine construct in an attempt to evaluate the synergy effect of combining multiple adjuvants. Physicochemical characterization demonstrated that the vaccine constructs folded differently and self-assembled into nanoparticles. Significantly, only vaccine constructs containing double copies of lipoamino acids (regardless in conjugation with Q11 or not) were capable to induce significant dendritic cells uptake and subsequent J14-specific antibody responses in non-sizes dependent manners. Q11 had minimal impact in enhancing the immunogenicity of J14 even when it was used in combination with lipoamino acids. These findings highlight the impact of lipoamino acids moiety as a promising immunostimulant carrier and its number of attachment to peptide epitope was found to have a profound effect on the vaccine immunogenicity.

Matched MeSH terms: Adjuvants, Immunologic/chemistry*

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