Inclusion of the Guinea Pig Cytomegalovirus Pentameric Complex in a Live Virus Vaccine Aids Efficacy against Congenital Infection but Is Not Essential for Improving Maternal and Neonatal Outcomes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Guinea Pigs
2.2. Virus and Cells
2.3. Generation of Live, Attenuated Vaccines
2.4. Study Design
2.5. ELISA and Neutralization Assay
2.6. Real-Time PCR Analyses
2.7. Sequence Analysis of Congenitally Transmitted Virus
2.8. Statistical Analyses
3. Results
3.1. Generation of Attenuated Vaccines and Evaluation for DNAemia Following Immunization
3.2. ELISA and Neutralization Responses
3.3. Pregnancy Outcomes after GPCMV Challenge
3.4. Congenital GPCMV Transmission and Pup Viral Load Analyses
3.5. Pups Were Congenitally Infected with SG-GPCMV Challenge Virus, and Not the Vaccine Virus
4. Discussion
5. Conclusions
- The inclusion of the GPCMV PC in a preconception live virus vaccine (PC/intact), compared to a PC/null virus, resulted in improved protection against vertical transmission of the virus (5/44 versus 16/46, p = 0.01).
- PC-intact wild-type virus vaccine was more likely to cause viremia post-immunization (5/12 animals), compared to animals immunized with attenuated PC/null and 3DX/Δ145 viruses (3/33; p < 0.05).
- PC/intact vaccine demonstrated enhanced humoral immunogenicity by ELISA compared to the 3DX/Δ145 vaccine virus.
- Dams in the PC/intact vaccine group demonstrated higher mean virus-neutralizing antibody titers, assessed on fibroblast cells, compared to either the PC/null or the 3DX/Δ145 groups.
- All vaccines evaluated in this study protected against maternal DNAemia and pup mortality.
- When congenital transmission occurred following SG-GPCMV challenge in immunized dams, sequence analysis indicated transmission occurred with wild-type (SG-GPCMV) virus and not vaccine virus.
- The presence of PC is insufficient, in and of itself, in conferring protection against vertical GPCMV transmission, compared to PC/intact wild-type virus vaccine, in the context of a 3DX [NK evasin]/Δ145 [PKR evasin] double deletion attenuated viral vaccine.
- Live attenuated and DISC virus CMV vaccination strategies represent a trade-off between the risk of unacceptable reactogenicity and impaired immunogenicity due to over-attenuation. The GPCMV model may prove useful in identifying attenuation strategies that confer protective immune responses, while at the same time improving safety, in future studies.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Vaccine Group | Vaccinated | Pregnant | Total Pups | Live Pups | Pup Mortality | Pup Weight (Grams) | Congenital GPCMV Transmission | Pregnancy Duration Post-SG-GPCMV Challenge |
---|---|---|---|---|---|---|---|---|
PBS (Control) | 12 | 11 | 40 | 11 | 73% | 84.5 ± 2.4 | 90% (36/40) | 24.1 ± 1.2 days |
PC/Intact | 12 | 12 | 44 | 43 | 2.3% * | 96 ± 2.3 | 11% (5/44) ** | 20.8 ± 1.2 days |
PC/Null | 12 | 12 | 46 | 44 | 4.3% * | 97.6 ± 1.9 | 35% (16/46) **,§ | 21.3 ± 1.3 days |
3DX/Δ145 | 12 | 11 | 40 | 36 | 10% * | 93 ± 1.7 | 76% (29/38) *** | 20.9 ± 1.3 days |
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Schleiss, M.R.; Fernández-Alarcón, C.; Hernandez-Alvarado, N.; Wang, J.B.; Geballe, A.P.; McVoy, M.A. Inclusion of the Guinea Pig Cytomegalovirus Pentameric Complex in a Live Virus Vaccine Aids Efficacy against Congenital Infection but Is Not Essential for Improving Maternal and Neonatal Outcomes. Viruses 2021, 13, 2370. https://doi.org/10.3390/v13122370
Schleiss MR, Fernández-Alarcón C, Hernandez-Alvarado N, Wang JB, Geballe AP, McVoy MA. Inclusion of the Guinea Pig Cytomegalovirus Pentameric Complex in a Live Virus Vaccine Aids Efficacy against Congenital Infection but Is Not Essential for Improving Maternal and Neonatal Outcomes. Viruses. 2021; 13(12):2370. https://doi.org/10.3390/v13122370
Chicago/Turabian StyleSchleiss, Mark R., Claudia Fernández-Alarcón, Nelmary Hernandez-Alvarado, Jian Ben Wang, Adam P. Geballe, and Michael A. McVoy. 2021. "Inclusion of the Guinea Pig Cytomegalovirus Pentameric Complex in a Live Virus Vaccine Aids Efficacy against Congenital Infection but Is Not Essential for Improving Maternal and Neonatal Outcomes" Viruses 13, no. 12: 2370. https://doi.org/10.3390/v13122370
APA StyleSchleiss, M. R., Fernández-Alarcón, C., Hernandez-Alvarado, N., Wang, J. B., Geballe, A. P., & McVoy, M. A. (2021). Inclusion of the Guinea Pig Cytomegalovirus Pentameric Complex in a Live Virus Vaccine Aids Efficacy against Congenital Infection but Is Not Essential for Improving Maternal and Neonatal Outcomes. Viruses, 13(12), 2370. https://doi.org/10.3390/v13122370