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Published on: May 2, 2011
Immunogenicity and protective efficacy of an RSV G S177Q central conserved domain nanoparticle vaccine
Harrison C Bergeron1, Jackelyn Murray1, Maria G Juarez2
1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Insights
A modified Respiratory Syncytial Virus (RSV) nanoparticle vaccine (NP-S177Q) demonstrated enhanced immunogenicity and neutralizing antibodies in mice compared to the wild-type version. Further development of this RSV vaccine candidate is supported by these findings.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Respiratory Syncytial Virus (RSV) causes significant lower respiratory tract disease in infants and the elderly.
- Despite extensive research, a safe and effective RSV vaccine remains unavailable.
- Previous studies indicated that a specific mutation (S177Q) in the RSV G glycoprotein's central conserved domain (CCD) enhances immunogenicity.
Purpose of the Study:
- To evaluate nanoparticle (NP) vaccines containing either wild-type (NP-WT) or mutated (NP-S177Q) RSV G protein CCD.
- To assess the immunogenicity and protective efficacy of these NP vaccine candidates adjuvanted with monophosphoryl lipid A (MPLA).
Main Methods:
- BALB/c mice were primed with NP-WT or NP-S177Q vaccines.
- Mice received a booster dose of either NP-WT or NP-S177Q vaccine.
- Vaccinated mice were subsequently challenged with RSV A2 to evaluate immune responses and protection.
Main Results:
- NP-S177Q boosting resulted in superior immunogenicity and higher levels of neutralizing antibodies compared to NP-WT boosting.
- Both NP-WT and NP-S177Q vaccines induced comparable neutralizing antibodies against RSV.
- NP-S177Q vaccination improved correlates of protection, including reduced lung inflammation, but revealed challenges with NP vaccine solubility and Th1-type responses.
Conclusions:
- The NP-S177Q vaccine candidate shows promise for further development due to improved immunogenicity and antibody responses.
- Optimization of the NP vaccine platform is necessary to address solubility and immune response balance issues.
Introduction:
Respiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity.
Methods:
Here, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2.
Results:
The results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response.
Discussion:
The results from this study support further NP-S177Q vaccine candidate development.
