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Analysis of Iophenoxic Acid Analogues in Small Indian Mongoose (Herpestes Auropunctatus) Sera for Use as an Oral Rabies Vaccination Biological Marker
Published on: May 31, 2019
A comparison of DNA vaccines for the rabies-related virus, Mokola
L H Nel1, M Niezgoda, C A Hanlon
1Centers for Disease Control and Prevention, Rabies Section MS-G33, 1600 Clifton road NE, Atlanta, GA 30333, USA. lhnel@postino.up.ac.za
Abstract:
Mokola virus, a rabies-related virus, has been reported to date from the African continent only. Like rabies virus, it is highly pathogenic, causes acute encephalitis, and zoonotic events have been documented. Although believed to be rare, there has been an unexplained increase in the number of isolations of the virus in South Africa in recent years. We have cloned and sequenced the glycoprotein (G) and nucleoprotein (N) genes from a South African Mokola virus, and used these in the construction of different DNA vaccines for immunization against Mokola virus. Four vaccines, utilizing different promoters and DNA backbone compositions, were generated and compared for efficacy in protection against Mokola virus. In one of these, both the Mokola virus G and N genes were co-expressed. Two of the single G-expressing DNA vaccines (based on pSG5 and pCI-neo, respectively) protected laboratory mice against lethal challenge, despite major differences in their promoters. However, neither vaccine was fully protective in a single immunization only. Serological assays confirmed titers of virus-neutralizing antibodies after immunization, which increased upon booster vaccine administration. A third construct (based on pBudCE4) was less effective in inducing a protective immune response, despite employing a strong CMV enhancer/promoter also used in the pCI-neo plasmid. Dual expression of Mokola virus G and N genes in pBudCE4 did not enhance its efficacy, under the conditions described. In addition, no significant utility could be demonstrated for a combined prime-boost approach, as no cross-protective immunity was observed against rabies or Mokola viruses from the use of pSG5-mokG or vaccinia-rabies glycoprotein recombinant virus vaccines, respectively, even though both vaccines provided 60-100% protection against homologous virus challenge.
Insights
Developing DNA vaccines against Mokola virus, a rabies relative, showed partial protection in mice. Some vaccines expressing the glycoprotein gene offered protection, but a single dose was insufficient. Booster doses increased antibody titers.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Mokola virus, a rabies-related virus endemic to Africa, is highly pathogenic and causes encephalitis.
- Recent unexplained increases in Mokola virus isolations in South Africa warrant further investigation.
- Zoonotic events involving Mokola virus have been documented, highlighting public health concerns.
Purpose of the Study:
- To develop and evaluate DNA vaccines for immunization against Mokola virus.
- To compare the efficacy of different DNA vaccine constructs utilizing various promoters and backbones.
- To assess the potential for co-expression of Mokola virus G and N genes in vaccine efficacy.
Main Methods:
- Cloning and sequencing of Mokola virus glycoprotein (G) and nucleoprotein (N) genes from a South African isolate.
- Construction and testing of four distinct DNA vaccine candidates with varying promoters and DNA backbones.
- Evaluation of vaccine efficacy in laboratory mice through lethal challenge studies and serological assays for virus-neutralizing antibodies.
Main Results:
- Two single G-expressing DNA vaccines (pSG5-mokG and pCI-neo-mokG) conferred partial protection against lethal Mokola virus challenge in mice.
- Neither vaccine provided full protection after a single immunization; booster doses increased virus-neutralizing antibody titers.
- A third construct (pBudCE4-mokG) showed reduced efficacy, and co-expression of G and N genes did not improve protection.
- Prime-boost strategies did not induce cross-protective immunity against rabies or Mokola viruses.
Conclusions:
- DNA vaccines expressing Mokola virus glycoprotein can induce partial protection and virus-neutralizing antibodies in mice.
- Optimizing DNA vaccine constructs, including promoter choice and backbone, is crucial for efficacy.
- Further research is needed to achieve full protection and explore cross-protective immunity against related rhabdoviruses.
