A small study involving 266 children, who had received two doses of a live, attenuated Japanese encephalitis vaccine SA-14-14-2 made in China, found very low levels of neutralising antibodies IgG at different time points after vaccination. It did not measure cell-mediated immune responses (T-cell immune responses).
The results are in line with other studies conducted outside India, which too found a decline in neutralising antibody levels post-vaccination. The results were recently published in The Journal of Travel Medicine.
While outbreaks of Japanese encephalitis are reported from several places in India, the disease burden is highest in Gorakhpur region of eastern Uttar Pradesh. Immunisation of children with the Chinese vaccine began in 2006 in 11 endemic regions, and became a part of the Universal Immunisation Programme in 181 endemic districts in 2011 first with a single dose and subsequently (2013) with two doses. Despite vaccination, there have been several outbreaks in the endemic regions, particularly in Gorakhpur district.
No longitudinal study
The study carried out in six villages in Gorakhpur district was not longitudinal (where the same set of children are studied at different time intervals). Instead, samples were collected from different children at different time points post two doses to provide a snapshot of the immune responses at specific time frames post-vaccination — 0-2 years, 2-4 years, 4-6 years, 6-8 years and 8-10 years.
In the absence of a longitudinal study, sampling children at different time points post-vaccination is the next best option to understand the durability of neutralising antibodies, says Dr. Priya Abraham, Professor in the Department of Clinical Virology, CMC Vellore, and a co-author of the paper.
The study found seroprevalence of IgG antibodies, and thus, seroprotection against the virus “decreased in the vaccinated children”. Nearly 98% of the children who received the vaccine did not have any IgG antibodies against the virus. The geometric mean titre was low even among children who received the vaccine 0-2 years prior to the study. Similar results were seen in a study carried out in Bangladesh, where children were immunised with the Chinese vaccine.
Does the absence of IgG responses in about 98% of the children studied reflect a complete lack of protection from infection, and hence the usefulness of the vaccine? “Cell-mediated responses need to be studied before any conclusions can be made,” Dr. Abraham says in an email to The Hindu. “We need to bear in mind the small sample size in this study. Also, follow-up of these children and lack of information about maintenance of the cold chain of the vaccine needs to be borne in mind.”
Benefits of Jenvac
In contrast, a trial carried out using an inactivated vaccine (Jenvac), developed by Bharat Biotech in collaboration with NIV Pune using a virus strain collected in India, has found superior protection at the end of two years even with a single dose. Jenvac has been approved as a single-dose vaccine; two doses of Jenvac are used as part of the Universal Immunisation Programme.
In the head-to-head comparison trial (published in November 2020) using Jenvac and the Chinese vaccine, the seroprotection at the end of one year and two years was 81.7% and 88.5% for Jenvac and just 47.9% and 68.3% for the Chinese vaccine, respectively.
The November 2020 trial also found significantly higher neutralising antibodies when children received two doses of Jenvac rather than two doses of the Chinese vaccine. And children who received Jenvac as the first dose and the Chinese vaccine as the second dose had higher antibody levels than those who received the Chinese vaccine as the first dose followed by Jenvac for the second dose.
The authors of the latest study have proposed a booster dose to improve the protection levels in children who have been fully vaccinated. But considering that the November 2020 trial found that two doses of Jenvac produced more antibodies than two doses of the Chinese vaccine, why should children be boosted with the Chinese vaccine, and why should the Chinese vaccine be used even for primary vaccination?
“Calling for complete stoppage of this [Chinese] vaccine would be premature, given some of the stated limitations of our study. However, our study clearly points to a marked decline of antibodies with time from receiving two doses of the vaccine,” says Dr. Abraham.
High seroprotection
Also, the second dose coverage at just 42% compared with 75% for the first dose makes a strong case for making a switch to Jenvac as even one dose had conferred far higher seroprotection than the Chinese vaccine.
“Our study is likely to prompt the government to organise a larger study. The findings will [have an] impact on the decisions made by policy makers regarding the future JE vaccination strategy for the country. Another study has shown potent specific T cell response to this vaccine in mice,” she says. “The present study as well as larger studies from other endemic regions in our country will help decide future vaccine strategies, particularly regarding the shift to other vaccines and different vaccination schedules.”
Published - March 11, 2023 08:15 pm IST
