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Incorporation of a GPI-anchored engineered cytokine as a molecular adjuvant enhances the immunogenicity of HIV VLPs.

Feng H, Zhang H, Deng J, Wang L, He Y, Wang S, Seyedtabaei R, Wang Q, Liu L, Galipeau J, Compans RW, Wang BZ - Sci Rep (2015)

Bottom Line: Co-delivery of mucosal adjuvants has been shown to be essential to induce effective mucosal immunity by non-replicating vaccines.A novel cytokine, GIFT4, engineered by fusing GM-CSF and interleukin-4, was previously found to simulate B cell proliferation and effector function.Incorporation of GPI-anchored GIFT4 into VLPs as a molecular adjuvant represents a novel approach to increase their immunogenicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.

ABSTRACT
HIV vaccines should elicit immune responses at both the mucosal portals of entry to block transmission and systemic compartments to clear disseminated viruses. Co-delivery of mucosal adjuvants has been shown to be essential to induce effective mucosal immunity by non-replicating vaccines. A novel cytokine, GIFT4, engineered by fusing GM-CSF and interleukin-4, was previously found to simulate B cell proliferation and effector function. Herein a membrane-anchored form of GIFT4 was constructed by fusing a glycolipid (GPI)-anchoring sequence and incorporated into Env-enriched HIV virus-like particles (VLPs) as a molecular adjuvant. Guinea pigs were immunized with the resulting HIV VLPs through an intramuscular priming-intranasal boosting immunization route. The GIFT4-containing VLPs induced higher levels of systemic antibody responses with significantly increased binding avidity and improved neutralizing breadth and potency to a panel of selected strains, as well as higher levels of IgG and IgA at several mucosal sites. Thus, the novel GPI-GIFT4-containging VLPs have the potential to be developed into a prophylactic HIV vaccine. Incorporation of GPI-anchored GIFT4 into VLPs as a molecular adjuvant represents a novel approach to increase their immunogenicity.

No MeSH data available.


Related in: MedlinePlus

Mucosal antibody endpoint titers.Mucosal samples were collected at week 12, 4 weeks after the last boosting immunization. Env-specific IgG and IgA endpoint titers were detected by ELISA as described in Materials and Methods. a, saliva IgG; b, saliva IgA; c, vaginal IgG; d, Vaginal IgA. Data were depicted as means ± standard deviations. *P < 0.05; **P < 0.01.
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f4: Mucosal antibody endpoint titers.Mucosal samples were collected at week 12, 4 weeks after the last boosting immunization. Env-specific IgG and IgA endpoint titers were detected by ELISA as described in Materials and Methods. a, saliva IgG; b, saliva IgA; c, vaginal IgG; d, Vaginal IgA. Data were depicted as means ± standard deviations. *P < 0.05; **P < 0.01.

Mentions: It is well established that mucosal immunity is essential for controlling a primary HIV-1 infection. In the present study, we employed an immunization regimen that contained one i.m. prime supplemented by two i.n. boosts, which was expected to elicit enhanced mucosal immune responses. To determine whether cVLPs induce enhanced mucosal immune responses by this immunization regimen, we evaluated the secretory Env-specific IgA and IgG levels in saliva and vaginal washes after three immunizations. As shown in Fig. 4a,b, both Env-specific IgG and IgA titers in saliva samples were found to be much higher in the cVLP group than that in the sVLP group. Remarkably, at week 10, cVLP-immunized guinea pigs also showed about 5-fold higher IgG levels (Fig. 4c) and 6-fold higher IgA levels (Fig. 4d) in vaginal washes than those induced in sVLP-immunized guinea pigs, demonstrating that the GIFT4 is an effective adjuvant for eliciting mucosal immune responses.


Incorporation of a GPI-anchored engineered cytokine as a molecular adjuvant enhances the immunogenicity of HIV VLPs.

Feng H, Zhang H, Deng J, Wang L, He Y, Wang S, Seyedtabaei R, Wang Q, Liu L, Galipeau J, Compans RW, Wang BZ - Sci Rep (2015)

Mucosal antibody endpoint titers.Mucosal samples were collected at week 12, 4 weeks after the last boosting immunization. Env-specific IgG and IgA endpoint titers were detected by ELISA as described in Materials and Methods. a, saliva IgG; b, saliva IgA; c, vaginal IgG; d, Vaginal IgA. Data were depicted as means ± standard deviations. *P < 0.05; **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493578&req=5

f4: Mucosal antibody endpoint titers.Mucosal samples were collected at week 12, 4 weeks after the last boosting immunization. Env-specific IgG and IgA endpoint titers were detected by ELISA as described in Materials and Methods. a, saliva IgG; b, saliva IgA; c, vaginal IgG; d, Vaginal IgA. Data were depicted as means ± standard deviations. *P < 0.05; **P < 0.01.
Mentions: It is well established that mucosal immunity is essential for controlling a primary HIV-1 infection. In the present study, we employed an immunization regimen that contained one i.m. prime supplemented by two i.n. boosts, which was expected to elicit enhanced mucosal immune responses. To determine whether cVLPs induce enhanced mucosal immune responses by this immunization regimen, we evaluated the secretory Env-specific IgA and IgG levels in saliva and vaginal washes after three immunizations. As shown in Fig. 4a,b, both Env-specific IgG and IgA titers in saliva samples were found to be much higher in the cVLP group than that in the sVLP group. Remarkably, at week 10, cVLP-immunized guinea pigs also showed about 5-fold higher IgG levels (Fig. 4c) and 6-fold higher IgA levels (Fig. 4d) in vaginal washes than those induced in sVLP-immunized guinea pigs, demonstrating that the GIFT4 is an effective adjuvant for eliciting mucosal immune responses.

Bottom Line: Co-delivery of mucosal adjuvants has been shown to be essential to induce effective mucosal immunity by non-replicating vaccines.A novel cytokine, GIFT4, engineered by fusing GM-CSF and interleukin-4, was previously found to simulate B cell proliferation and effector function.Incorporation of GPI-anchored GIFT4 into VLPs as a molecular adjuvant represents a novel approach to increase their immunogenicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.

ABSTRACT
HIV vaccines should elicit immune responses at both the mucosal portals of entry to block transmission and systemic compartments to clear disseminated viruses. Co-delivery of mucosal adjuvants has been shown to be essential to induce effective mucosal immunity by non-replicating vaccines. A novel cytokine, GIFT4, engineered by fusing GM-CSF and interleukin-4, was previously found to simulate B cell proliferation and effector function. Herein a membrane-anchored form of GIFT4 was constructed by fusing a glycolipid (GPI)-anchoring sequence and incorporated into Env-enriched HIV virus-like particles (VLPs) as a molecular adjuvant. Guinea pigs were immunized with the resulting HIV VLPs through an intramuscular priming-intranasal boosting immunization route. The GIFT4-containing VLPs induced higher levels of systemic antibody responses with significantly increased binding avidity and improved neutralizing breadth and potency to a panel of selected strains, as well as higher levels of IgG and IgA at several mucosal sites. Thus, the novel GPI-GIFT4-containging VLPs have the potential to be developed into a prophylactic HIV vaccine. Incorporation of GPI-anchored GIFT4 into VLPs as a molecular adjuvant represents a novel approach to increase their immunogenicity.

No MeSH data available.


Related in: MedlinePlus