Journal of Antivirals & Antiretrovirals
Open Access

Measles Virus as a Vector for the HPV Vaccine Development

Narayana Penta^*, Gaurav Gupta and Reinhard Glueck ^*Correspondence: Narayana Penta, Vaccine Research and Development Division, Zydus Cadila Healthcare Limited,, Ahmedabad, India, Email:

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Description

Modern approaches in vaccinology and immunology have led to the discovery of a number of antigens potentially allowing addressing complex diseases such as AIDS, cancer and malaria, if administered in an appropriate way. Therefore, the establishment of potent antigen delivery systems became essential for the progress in this field. The use of live attenuated viral vectors appears promising especially since multiple antigens can efficiently be presented to the immune system. Attenuated Measles Virus (MV) vaccine represents a number of essential features for the development of candidate prophylactic and therapeutic vaccines. Among these features are safeties, immunogenicity and cost effectiveness of the recombinant vaccines.

MV belongs to the genus Morbillivirus in the family Paramyxoviridae. It is an enveloped virus with a long nonsegmented RNA genome of negative polarity [1]. In 1954, Enders and Peebles inoculated primary human kidney cells with the blood of David Edmonston, a child with measles and the resulting Edmonston strain of MV was subsequently adapted to growth in a variety of cell lines. Adaptation to chicken embryos, chick embryo fibroblasts (CEF), and/or dog kidney cells and human diploid cells produced the attenuated Edmonston A and B, Zagreb (EZ) and AIK-C seeds [2]. Edmonston-B was licensed in 1963 as the first MV vaccine. However, being reactogenic it was abandoned in 1975. Further passages of Edmonston A and B on CEF produced the more attenuated Moraten vaccines [3]. Today, the Schwarz/Moraten, AIK-C and EZ vaccines are commonly used. An MV vaccine induces a lifelong immunity after a single or two low-dose injections. Persistence of antibodies and CD8 cells has been shown for as long as 25 years after vaccination. MV vaccines are easily produced on a large scale in most countries and can be distributed at low cost. Because the attenuation of MV genome results from an advantageous combination of numerous mutations, the vaccine is very stable and reversion to pathogenicity has never been observed. Regarding safety, MV replicates exclusively in the cytoplasm, ruling out the possibility of integration into host DNA. These characteristics make live attenuated MV vaccine an attractive candidate for use as a multivalent vaccination vector.

A reverse genetics system for MV was established allowing the rescue of infectious MV from cloned cDNA [4]. Additional MVspecifc transcription units containing multiple cloning sites were introduced into the MV antigenome (i.e. cDNAsequence) allowing the addition and simultaneous expression of several exogenous genes. Genes from Hepatitis B Virus (HBV), Simian or Human Immunodeficiency Viruses (SIV, HIV), Mumps virus (MV), West Nile Virus (WNV) and human IL12 were inserted and expressed from different loci of the MV genome. Here we show that multiple marker genes coding for Chloramphenicol Acetyltransferase (CAT), Green Fluorescent Protein (GFP) and Betagalactosidase (B-gal) can be expressed simultaneously by the same progeny. In addition, recombinant MVs expressing single or multiple antigens of SIV induced strong and enduring humoral immune responses in experimental animals.

References

1. Enders JF, Peebles TC. Propagation in tissue cultures of cytopathogenic agents from patients with measles. Proc Soc Exp Biol Med. 1954; 86:277-286.
2. Hilleman MR. Current overview of the pathogenesis and prophylaxis of measles with focus on practical implications. Vaccine. 2002; 20:651-665.
3. Rota J, Wang Z, Rota AP, Bellini W. Comparison of sequences of the H, F and N coding genes of measles virus vaccine strains. Virus Res. 1994; 31:317-330.
4. Schwarz A. Preliminary tests of a highly attenuated measles vaccine. Am J Dis Child. 1962; 103:216-219.