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Vaccine with bacterium-like particles displaying HIV-1 gp120 trimer elicits specific mucosal responses and neutralizing antibodies in rhesus macaques |
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| Authors: | Huaiyu Wang Pingchao Li Mo Zhang Jinpeng Bi Yizi He Fangshen Li Rongzhen Yu Feng Gao Wei Kong Bin Yu Ling Chen Xianghui Yu |
| Institution: | 1. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012 China
These authors contributed equally to this work.;2. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou, 510530 China These authors contributed equally to this work.;3. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012 China;4. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou, 510530 China University of Chinese Academy of Sciences, Beijing, 100049 China;5. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012 China Department of Medicine, Duke University Medical Center, Durham, NC, 27710 USA;6. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012 China Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012 China;7. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou, 510530 China |
| Abstract: | Preclinical studies have shown that the induction of secretory IgA (sIgA) in mucosa and neutralizing antibodies (NAbs) in sera is essential for designing vaccines that can effectively block the transmission of HIV-1. We previously showed that a vaccine consisting of bacterium-like particles (BLPs) displaying Protan-gp120AE-MTQ (PAM) could induce mucosal immune responses through intranasal (IN) immunization in mice and NAbs through intramuscular (IM) immunization in guinea pigs. Here, we evaluated the ability of this vaccine BLP-PAM to elicit HIV-1-specific mucosal and systemic immune responses through IN and IM immunization combination strategies in rhesus macaques. First, the morphology, antigenicity and epitope accessibility of the vaccine were analysed by transmission electron microscopy, bio-layer interferometry and ELISA. In BLP-PAM-immunized macaques, HIV-1-specific sIgA were rapidly induced through IN immunization in situ and distant mucosal sites, although the immune responses are relatively weak. Furthermore, the HIV-1-specific IgG and IgA antibody levels in mucosal secretions were enhanced and maintained, while production of serum NAbs against heterologous HIV-1 tier 1 and 2 pseudoviruses was elicited after IM boost. Additionally, situ mucosal responses and systemic T cell immune responses were improved by rAd2-gp120AE boost immunization via the IN and IM routes. These results suggested that BLP-based delivery in combination with the IN and IM immunization approach represents a potential vaccine strategy against HIV-1. |
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