DNA vaccination with both the haemagglutinin and fusion proteins but not the nucleocapsid protein protects against experimental measles virus infection

Abstract

Plasmids that expressed the nucleocapsid, haemagglutinin and fusion proteins of measles virus (MV) were used to immunize cotton rats (Sigmodon hispidus) against intranasal MV infection. After immunization with all three plasmids, T cell responses and MV-specific antibodies were induced. A reduction in virus titre was observed in lung tissue from animals immunized with plasmids expressing the viral glycoproteins. Histologically, however, a moderate peribronchitis was observed after immunization with the plasmid expressing the fusion protein whereas, after immunization with plasmids expressing haemagglutinin or both glycoproteins, only mild or focal peribronchitis was seen. Immunization with the nucleocapsid did not reduce virus titres, probably because of the failure to induce neutralizing antibodies. A disadvantage of plasmid immunization was its inefficacy in the presence of MV-specific ' maternal' antibodies. This indicates that genetic immunization has to be improved to be a useful alternative vaccine against measles.Measles is still one of the most serious infectious diseases worldwide. Although a live-attenuated vaccine virus exists, roughly one million children die of measles virus (MV) infection every year, mostly in developing countries (Katz, 1995). Immunization at an early age is necessary in order to protect infants against infection. However, because of maternal antibodies, vaccine-induced seroconversion is often inhibited (Griffin, 1995). In addition, because of the immaturity of the neonatal immune system, early immunization in the absence of maternal antibodies results in inadequate levels of immune protection. As the WHO has set the eradication of MV as a public health goal, alternative vaccine candidates are needed (Wild, 1999).

Neonatal Immunization with a Sindbis Virus-DNA Measles Vaccine Induces Adult-Like Neutralizing Antibodies and Cell-Mediated Immunity in the Presence of Maternal Antibodies

“…Such a prime-boost strategy could protect very young infants in developing countries against measles infection during the first year of life. 4 Ags have been pursued as promising measles vaccine candidates. Several studies have shown a degree of protective efficacy using a variety of DNA plasmids encoding MV hemagglutinin and fusion glycoproteins in cotton rats (3,4) and rhesus macaques (5)(6)(7).…”

Protective immunity of single and multi-antigen DNA vaccines against schistosomiasis

“…has been studied in different animal model and for different parasites, such as, Schistosoma (Mohamed et al 1998), Plasmodium (Grifantini et al 1998), Leishmania (Xu et al 1995) and Mycobacterium (Morris et al 2000); virus, as rabies (Lodmell et al 1998), herpes (Sin et al 2000), hepatitis C (Arichi et al 2000), influenza (Dégano et al 2000, Johnson et al 2000, dengue (Raviprakash et al 2000), measles (Schlereth et al 2000), cytomegalovirus (Morello et al 2000); as well as for melanoma (Xiang et al 2000), and immune diseases, such as encefalomielitis (Weissert et al 2000).…”

Measles Virus-Specific CD4 T-Cell Activity Does Not Correlate with Protection against Lung Infection or Viral Clearance

“…fection (29). On the other hand, neutralizing antibodies against the hemagglutinin protein are protective against infection.…”

“…For DNA vaccination plasmids pSC-N (nucleocapsid protein), pCG-F1 (fusion protein), or pCG-H5 (hemagglutinin) (29) were used. Plasmid DNA was purified using a plasmid Maxi kit (QIAGEN, Hilden, Germany).…”