A Japanese Encephalitis Vaccine From India Induces Durable and Cross-protective Immunity Against Temporally and Spatially Wide-ranging Global Field Strains

Abstract

CTRI/2011/07/001855.

Japanese encephalitis vaccines: Immunogenicity, protective efficacy, effectiveness, and impact on the burden of disease

“…In general, these studies have shown that NAb titres are highest against G-II and homologous G-III viruses, followed by G-IV and heterologous G-III viruses, whereas titres against G-I viruses are the lowest, and in some cases below protective levels. 22,[24][25][26][27][28][29] A recent study specifically evaluated the ability of a G-III virus to elicit protective responses in mice, and the ability of human post-vaccinal and acute phase sera to neutralize G-V viruses. The study found that (a) NAb titres in mice immunized with either G-III or G-V virus were higher with homologous viruses but poor against G-V, (b) the SA14-14-2 LAV or the P-3 inactivated vaccines were less protective against G-V virus challenge in mice, and (c) both GMTs and SPRs were poor against G-V virus, intermediate against G-I virus, and highest against G-III virus with both post-vaccinal and acute phase human sera.…”

“…179 With an Indian CCDI vaccine, it was shown that about two-thirds of the evaluated subjects carried protective NAb titres for up to at least 18 months. 29 The results on the longevity of responses should be interpreted with caution since the outcome may depend on whether the study was conducted in a non-endemic or an endemic area. Seropositivity rates are known to increase significantly beyond 10-15 years of age in endemic areas, 167,[180][181][182] and an inverse correlation has been observed between an age of >5-6 years and the incidence of JE disease.…”

“…Immunogenicity studies of 2 doses of this vaccine compared to a single dose of SA14-14-2 LAV vaccine showed that the former was better in all age groups ranging from 1 to 50 years, with SPRs of >90% after both the doses (immunized on days 0 and 28, and sera obtained at days 28 and 56), whereas SPRs for SA14-14-2 LAV vaccine were 77.6% and 60.3% at the same time-points following a single dose. 29 Although this difference was probably due to a combination of the single dose of SA14-14-2 vs. the 2 doses of the CCDI vaccine and the neutralization data being obtained with the strain used for the CCDI vaccine, it was found that the SRC, SRP and GMT were all higher for the homologous virus-sera pairs for the CCDI vaccine strain than the SA-14-14-2 LAV strain. 29 It has been noted that, compared to MBDI vaccines, the Vero cell-derived inactivated vaccine elicits markedly higher NAb responses, or that lower amounts of antigen are sufficient to elicit equivalent responses.…”

“…29 Although this difference was probably due to a combination of the single dose of SA14-14-2 vs. the 2 doses of the CCDI vaccine and the neutralization data being obtained with the strain used for the CCDI vaccine, it was found that the SRC, SRP and GMT were all higher for the homologous virus-sera pairs for the CCDI vaccine strain than the SA-14-14-2 LAV strain. 29 It has been noted that, compared to MBDI vaccines, the Vero cell-derived inactivated vaccine elicits markedly higher NAb responses, or that lower amounts of antigen are sufficient to elicit equivalent responses. 74,132,141,142,145 Although the factors responsible for this are not known, some of the suggested reasons for higher potency of CCDI vaccines are: (a) less bioprocess steps and milder down-stream processing conditions, (b) ultrastructural morphology of cell culture-derived vaccine virus being more similar than the MBDI vaccine virus to the native virus, (c) higher affinity toward several monoclonal antibodies, 141 and (d) differential glycosylation of the E protein.…”

“…encephalitis, 21 (b) the fact that vaccination has significantly reduced JE cases (see below), and (c) studies of in vitro neutralization of heterologous genotype viruses by sera from subjects immunized with any one of the genotype viruses. 17,[22][23][24][25][26][27][28][29] Types G-I to G-IV have been frequently detected whereas G-V is relatively rare. 30 Viruses belonging to G-I have been reported from Australia, Cambodia, China, India, Japan, Malaysia, South Korea, northern parts of Thailand, and Vietnam; G-II has been reported from Australia, Indonesia, Malaysia (especially Sarawak), Papua New Guinea, South Korea, and southern parts of Thailand; G-III has been reported from China, India, Japan, Nepal, The Philippines, South Korea, Sri Lanka, and Taiwan; G-IV has been reported from Indonesia; G-V has been reported from China, Malaysia, and South Korea 31,32 It should be noted that in most endemic countries, more than one genotype may circulate simultaneously, with possible periodic changes in dominant genotypes.…”