Induction of mucosal immunity against pathogens by using recombinant baculoviral vectors: Mechanisms, advantages, and limitations

Fragoso-Saavedra, Mario; Vega-Lopez, M. A.

doi:10.1002/jlb.4mr0320-488r

Cited by 6 publications

(7 citation statements)

References 186 publications

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“…A robust mucosal immune response, characterized by antibody responses in the intestines, would act as a barrier and limit T. gondii transgressions into the epithelial cells. Baculovirus-based vaccines are capable of inducing mucosal immunity against various mucosal pathogens, as demonstrated using the influenza virus and the human papillomavirus ( Fragoso-Saavedra and Vega-López, 2020 ). Consistent with these findings, the ROP4-rBV vaccine generated in this study successfully induced mucosal antibody responses, especially intestinal IgG and IgA which contributed to protection against a lethal dose of T. gondii ME49 infection.…”

Section: Discussionmentioning

confidence: 99%

Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice

Yoon

Chu

Kang

et al. 2021

Front. Cell. Infect. Microbiol.

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Pathogens require physical contact with the mucosal surface of the host organism to initiate infection and as such, vaccines eliciting both mucosal and systemic immune responses would be promising. Studies involving the use of recombinant baculoviruses (rBVs) as mucosal vaccines are severely lacking despite their inherently safe nature, especially against pathogens of global importance such as Toxoplasma gondii. Here, we generated rBVs displaying T. gondii rhoptry protein 4 (ROP4) and evaluated their protective efficacy in BALB/c mice following immunization via intranasal (IN) and oral routes. IN immunization with the ROP4-expressing rBVs elicited higher levels of parasite-specific IgA antibody responses compared to oral immunization. Upon challenge infection with a lethal dose of T. gondii ME49, IN immunization elicited significantly higher parasite-specific antibody responses in the mucosal tissues such as intestines, feces, vaginal samples, and brain than oral immunization. Marked increases in IgG and IgA antibody-secreting cell (ASC) responses were observed from intranasally immunized mice. IN immunization elicited significantly enhanced induction of CD4+, CD8+ T cells, and germinal center B (GC B) cell responses from secondary lymphoid organs while limiting the production of the inflammatory cytokines IFN-γ and IL-6 in the brain, all of which contributed to protecting mice against T. gondii lethal challenge infection. Our findings suggest that IN delivery of ROP4 rBVs induced better mucosal and systemic immunity against the lethal T. gondii challenge infection compared to oral immunization.

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Section: Discussionmentioning

confidence: 99%

Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice

Yoon

Chu

Kang

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Recombinant viral vectors, including the baculovirus AcMNPV, elicit robust local immune responses when administered intranasally ( 18 , 32 ). To determine the best inoculation route to produce 3BT-specific antibodies in serum and mucosae, mini-pigs were immunized with virions of BacDual-3BT, either utilizing the combined s.c.-i.n.…”

Section: Resultsmentioning

confidence: 99%

“…For PRRSV-2, intranasal and parenteral live-attenuated vaccines have been evaluated, with the risk of mucosal shedding and reversion to virulence ( 95 , 103 , 104 ). Besides, experimental mucosal immunogens based on recombinant proteins, VLPs, or viral vectors have targeted PRRSV-2 surface glycoproteins, with the disadvantage of including decoy epitopes and glycan shields ( 30 , 32 ). Our rationale in choosing the conserved epitope B to design 3BT was based on studies in which peptide-binding and phage-display assays demonstrated that infection-elicited nAbs bind to epitope B in PRRSV-2 ( 75 , 77 , 105 ).…”

Section: Discussionmentioning

confidence: 99%

“…An alternative vector is the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), which only infects insects in nature ( 31 ). Besides, AcMNPV is an efficient vector for intranasal immunization in experimental settings, given the abundant CpG oligodeoxynucleotide content in its genome, among other immunogenic properties ( 32 ).…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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“…In addition, the intranasal or oral administration of a baculovirus-vectored human papillomavirus (HPV) vaccine conferred protection against vaginal HPV infection [ 50 , 51 ]. Mycobacterium bovis Bacillus Calmette–Guérin (BCG), the only licensed vaccine against TB, has been further developed as vaccine vectors against HIV-1 and SARS-CoV-2 [ 52 , 80 , 81 , 82 ].…”

Section: Challenges and Solutions For The Development Of Mucosa-targe...mentioning

confidence: 99%

Strategies to Develop a Mucosa-Targeting Vaccine against Emerging Infectious Diseases

Feng

Wen

Chen

et al. 2022

Viruses

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Numerous pathogenic microbes, including viruses, bacteria, and fungi, usually infect the host through the mucosal surfaces of the respiratory tract, gastrointestinal tract, and reproductive tract. The mucosa is well known to provide the first line of host defense against pathogen entry by physical, chemical, biological, and immunological barriers, and therefore, mucosa-targeting vaccination is emerging as a promising strategy for conferring superior protection. However, there are still many challenges to be solved to develop an effective mucosal vaccine, such as poor adhesion to the mucosal surface, insufficient uptake to break through the mucus, and the difficulty in avoiding strong degradation through the gastrointestinal tract. Recently, increasing efforts to overcome these issues have been made, and we herein summarize the latest findings on these strategies to develop mucosa-targeting vaccines, including a novel needle-free mucosa-targeting route, the development of mucosa-targeting vectors, the administration of mucosal adjuvants, encapsulating vaccines into nanoparticle formulations, and antigen design to conjugate with mucosa-targeting ligands. Our work will highlight the importance of further developing mucosal vaccine technology to combat the frequent outbreaks of infectious diseases.

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Induction of mucosal immunity against pathogens by using recombinant baculoviral vectors: Mechanisms, advantages, and limitations

Cited by 6 publications

References 186 publications

Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice

Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice

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

Strategies to Develop a Mucosa-Targeting Vaccine against Emerging Infectious Diseases

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