Nano-vaccines for gene delivery against HIV-1 infection

Figures & data

Figure 1. Different types of nano-vaccines for gene delivery used in the development of HIV-1 vaccines. (a) Gold nanorods (GNRs); (b) Silica-coated calcium phosphate nanoparticles (SCPs); (c) Poly(lactic-co-glycolic acid) (PLGA); (d) Polymethylmethacrylate (PMMA); (e) Lipid nanoparticles (LNPs); (f) Adenovirus (Ad); (g) Adeno-associated virus (AAV); (h) Lentivirus (LV); (i) Poxvirus.

Table 1. Non-viral vectored nano-vaccines against HIV-1.

Vector	Diameter	Encoding antigen	Immune response	Immunization route	Ref
GNRs	15 nm × 60 nm	Env	Humoral and cellular immune responses	s.c., i.m., i.p., or i.n.	[34]
SCPs	158.8 nm	SOSIP.664	Humoral and cellular immune responses	i.m. or s.c.	[38]
PLGA	300 ~ 500 nm	PCLUS3-18IIIB	Colorectal immune response and mucosal immunity	i.r.c. or s.c.	[47]
PMMA	~200 nm	Tat/Gag	Th1-type immune response and cytotoxic T lymphocyte response	i.m.	[49]
LNP	20 nm ~ 10 μm	Env	Humoral and cellular immune responses	i.d.	[54]

GNRs: gold nanorods; SCPs: Silica-coated calcium phosphate nanoparticles; PLGA: poly(lactic-co-glycolic acid); PMMA: polymethylmethacrylate; LNP: lipid nanoparticles; s.c.: subcutaneous; i.m.: intramuscular; i.p.: intraperitoneal; i.n.: intranasal; i.r.c.: intracolorectal; i.d.: intradermal.

Figure 2. Schematic illustrations of inorganic nano-vaccines for gene delivery against HIV-1. (a) The surface of GNRs was modified with CTAB, PDDAC, PEI, and pDNA. After the uptake of GNRs complexes, APCs, especially DCs, can phagocytose the GNRs complex and process the antigens. (b) The surface of calcium phosphate nanoparticles was modified with PEI, CpG, and pDNA. After the uptake of SCPs complexes, APCs, especially DCs, can be activated.

Figure 3. Transduction pathway of viral vectored nano-vaccines for gene delivery against HIV-1. The details of the trafficking pathway are not entirely clear. Viral vectors are thought to trigger internalization by endocytosis. The viral particles are transferred to the nucleus via the nuclear pore complex. In the nucleus, viral DNA is released by uncoating, followed by transcription and exporting messenger RNA for translation. The product of gene expression elicits HIV-1-specific immune responses after release.

Table 2. Viral vectored nano-vaccines against HIV-1.

Vector	Diameter	Encoding antigen	Immune response	Immunization route	Ref
Ad	70 ~ 90 nm	Env/Gag/Pol	Cytotoxic T cell response, humoral immune response, and ADCP response	i.m. or i.r.	[64–66]
AAV	20 ~ 26 nm	Env	Humoral and cellular immune responses	i.m.	[75,77]
LV	80 ~ 120 nm	Gag/Rev/Env	Cytotoxic T cell response and binding antibody response	i.m.	[85,86]
Poxvirus	(300 ~ 450) × (170 ~ 260) nm	Env	Binding antibody response	i.m.	[95–98]

Ad: adenovirus; AAV: adeno-associated virus; LV: lentivirus; i.m.: intramuscular; i.r.: intrarectal.

Figure 4. The presentation mechanisms of nano-vaccines for induction of immune responses against HIV-1. Nano-vaccine is transfected into target cells, followed by gene transcription and synthesis of encoded proteins. HIV-1 antigens are presented by APCs via MHC I molecules either directly transfecting vaccines or presenting by other cells. HIV-1 antigens are also presented on MHC II molecules when transfected cells secrete encoded proteins. Subsequently, APCs activate T cells by presenting antigens using MHC I and T cell receptors to induce HIV-1-specific T-cell immune responses. Otherwise, antigens are presented to CD4⁺ T cells via the MHC II pathway, inducing HIV-1-specific B cell responses.

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