No demonstrable association between the Leningrad-Zagreb mumps vaccine strain and aseptic meningitis in a large clinical trial in Egypt.

To address the claim that the Leningrad-Zagreb (L-Z) mumps vaccine strain is causally associated with aseptic meningitis, a prospective, post-marketing safety study was conducted with a measles-mumps-rubella vaccine (MMR) (TRESIVAC(R); Serum Institute of India Ltd., Pune, India), which uses the L-Z strain as its mumps component in Egypt. In all, 453 119 children (65 423 children aged 16-24 months and 329 211 children aged 5-7 years) received MMR. The control groups which, as a result of local health regulations, were slightly younger than vaccinees, comprised 12 253 and 46 232 children, respectively. Using questionnaires, the parents recorded solicited local, systemic and neurological adverse events for up to 42 days post-vaccination. All data were analysed externally on an intention-to-treat basis by individuals not participating in the study. Local and/or systemic reactions were reported in a small percentage of participants, with pain, fever and parotitis being the most common signs among vaccinees in both age groups. No case of aseptic meningitis, encephalitis, anaphylaxis or convulsions was observed in any participant. Thus, in this series of more than 450 000 Egyptian children, the L-Z mumps vaccine strain in this vaccine did not cause aseptic meningitis. The vaccine is considerably cheaper than Western competitors and a valid alternative to other MMR vaccines.

Persistence of antibodies induced by measles-mumps-rubella vaccine in children in India.

Antibody levels in 41 Indian girls were measured 6 years after measles-mumps-rubella (MMR) vaccination. Rates of seropositivity were 88% (measles antibodies), 95% (mumps antibodies), and 100% (rubella antibodies). The MMR vaccine induces long-term immunity in a majority of vaccinees; however, due to the observation of some seronegative vaccinees, the policy of administering a second dose of the MMR vaccine seems appropriate.

Immunogenicity of a new, low-cost recombinant hepatitis B vaccine derived from Hansenula polymorpha in adults.

BACKGROUND: Hepatitis B virus (HBV) infection is highly prevalent world over, especially in developing countries. A new recombinant hepatitis B virus (GeneVac-B; Serum Institute of India Ltd.) vaccine is developed using Hansenula polymorpha yeast. We decided to assess the immunogenicity, and reactogenicity of this vaccine in a large adult population. MATERIAL AND METHODS: Seven hundred eighty-eight adults subjects (age: 19-57 years, male:female ratio 35:1) received three 20 microg doses of a H. polymorpha-derived recombinant hepatitis B vaccine in months 0, 1, and 6. All the eligible subjects had negative baseline serum HBs Ag, and anti-HBs. The anti-HBs titer was obtained 1 month after the last dose of vaccine and was considered seroconverted if more than 1 mIU/ml, and seroprotective if more than 10 mIU/ml. RESULTS: The seroprotection rate was 96% and seroconversion rate was 97%. Seroconversion and seroprotection rates declined with increasing age. The minimum geometric mean titre of anti HBs was 443 mIU/ml (95% CI 407-482). Seroprotection was 96% in age group<40 years, while the same was 91% in >40 years group (Odd's ratio-2.9100, Z value-2.6183, highly significant). No other factor like smoking, tobacco-chewing, alcohol consumption, chronic diseases, and obesity, affected the immune response. No significant adverse reactions were reported in any of the subjects. CONCLUSIONS: Three standard doses of the H. polymorpha-derived recombinant HBV vaccine are highly immunogenic and safe in a predominantly male adult population. Young adults respond better with this vaccine. Because of its low cost, the vaccine may be a good choice in prevention of hepatitis B infection.

No definitive evidence for L-Zagreb mumps strain associated aseptic meningitis: a review with special reference to the da Cunha study.

The study by da Cunha et al. published in 2002 reported that MMR vaccine containing L-Zagreb mumps strain manufactured by Serum Institute of India Ltd. caused a high incidence of aseptic meningitis (AM) from routine surveillance during two mass immunization campaigns (MIC) conducted in 1998 in two states in Brazil. Since the results were contrary to those in India, Egypt and Bahamas, a critical analysis of the study was done. Several inconsistencies were found in the study, which undermined the conclusions drawn. Two similar studies from Brazil reported similar results. Review of these studies and those done on the vaccine from Zagreb, Croatia showed that in no study the L-Zagreb mumps virus has been isolated from cerebrospinal fluid (CSF) of an AM case. Isolation of the vaccine virus is necessary for definite causal association of AM with the vaccine. There is no such evidence to causally link MMR vaccine containing L-Zagreb mumps strain with AM.

DNA vaccine for rabies: relevance of the trans-membrane domain of the glycoprotein in generating an antibody response.

Various studies have demonstrated the potential of immunization with DNA vaccines encoding the rabies virus glycoprotein (RV-G) to elicit humoral responses. In the present study, we have designed four constructs using a VR1020 vector, wherein the RV-G ectodomain has been cloned without the signal sequence (SS) and the trans-membrane domain (TD) (rGVR), without the SS but with the TD (rGVRt), with the SS but without the TD (rGVRs) and with the SS and the TD (rGVRst), under the control of a cytomegalovirus (CMV) promoter, and downstream of the tissue plasminogen activator (TPA) signal sequence. In addition, RV-G has been expressed as a His6 tag fusion protein, both in Escherichia coli as well as in baculovirus expression systems. Using a prime-boost strategy, BALB/cJ mice administered with the rGVRt construct either in saline (intramuscularly) or adsorbed onto gold microcarriers (delivered intradermally by gene gun) generated the highest rabies virus neutralizing antibody (RVNA) titers. Inclusion of the SS, in addition to the TD (rGVRst), led to a significant decrease in RVNA titers, compared to the rGVRt construct. The DNA vaccine construct lacking both the SS and the TD domain and the vaccine having only the SS generated lower antibody responses, compared to the rGVRt construct. After priming with DNA vaccine, boosting with both E. coli- as well as baculovirus-expressed rRV-G led to an increase in the RVNA titers. The present results demonstrate that a DNA vaccine encoding the full-length sequence of the ectodomain plus TD of the mature native RV-G is capable of expressing an 'ideal' immunogen to produce RVNA titers.