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Comparative analysis of the immunogenicity of monovalent and multivalent rotavirus immunogens.

ABSTRACT: The strategies for developing rotavirus (RV) vaccines have always been controversial. At present, both the monovalent RV vaccine and the multivalent RV vaccine have displayed excellent safety and efficacy against RV infection and shown cross-reactive immunity, which laid the question whether the multivalent RV vaccine could be replaced by the monovalent RV vaccine. In this study, we focused on comparing the immunogenicity (serum neutralization activity and protection against homotypic and heterotypic RVs' challenge) of individual standard RV strains (monovalent RV immunogens) and different combinations of them (multivalent RV immunogens). In result, RV immunogens showed general immunogenicity and heterotypic reaction but the multivalent RV immunogens exhibited greater serum neutralization activity and stronger heterotypic reaction than the monovalent RV immunogens (P<0.05). As to the protection, the multivalent RV immunogens also revealed more rapid and stronger protection against homotypic and heterotypic RVs' challenge than the monovalent RV immunogens. The results demonstrated that both the monovalent and multivalent RV immunogens exhibited high immunogenicity, but the monovalent RV immunogens could not provide enough neutralization antibodies to protect MA104 cells against the infection with heterotypic RV strains and timely protection against homotypic and heterotypic RVs, so the multivalent RV vaccine could not be replaced by the monovalent RV vaccine.

SUBMITTER: Mi K

PROVIDER: S-EPMC5313208 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Comparative analysis of the immunogenicity of monovalent and multivalent rotavirus immunogens.

Mi Kai K Ou Xia X Guo Lili L Ye Jing J Wu Jinyuan J Yi Shan S Niu Xianglian X Sun Xiaoqin X Li Hongjun H Sun Maosheng M

PloS one 20170216 2

The strategies for developing rotavirus (RV) vaccines have always been controversial. At present, both the monovalent RV vaccine and the multivalent RV vaccine have displayed excellent safety and efficacy against RV infection and shown cross-reactive immunity, which laid the question whether the multivalent RV vaccine could be replaced by the monovalent RV vaccine. In this study, we focused on comparing the immunogenicity (serum neutralization activity and protection against homotypic and hetero ...[more]

PMID: 28207817

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Project description:Background and aimsROTAVAC® (frozen formulation stored at -20 °C) and ROTAVAC 5D® (liquid formulation stable at 2-8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia.MethodsWe conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89-12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose.ResultsThe study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period.ConclusionsAmong Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.

Project description:Current influenza vaccines need to be updated annually due to mutations in the globular head of the viral surface protein, hemagglutinin (HA). To address this, vaccine candidates have been designed based on the relatively conserved HA stem domain and have shown protective efficacy in animal models. Oligomerization of the antigens either by fusion to oligomerization motifs or display on self-assembling nanoparticle scaffolds, can induce more potent immune responses compared to the corresponding monomeric antigen due to multivalent engagement of B-cells. Since nanoparticle display can increase manufacturing complexity, and often involves one or more mammalian cell expressed components, it is important to characterize and compare various display and oligomerization scaffolds. Using a structure guided approach, we successfully displayed multiple copies of a previously designed soluble, trimeric influenza stem domain immunogen, pH1HA10, on the ferritin like protein, MsDps2 (12 copies), Ferritin (24 copies) and Encapsulin (180 copies). All proteins were expressed in Escherichia coli. The nanoparticle fusion immunogens were found to be well folded and bound to the influenza stem directed broadly neutralizing antibodies with high affinity. An 8.5 Å Cryo-EM map of Msdps2-pH1HA10 confirmed the successful design of the nanoparticle fusion immunogen. Mice immunization studies with the soluble trimeric stem and nanoparticle fusion constructs revealed that all of them were immunogenic, and protected mice against homologous (A/Belgium/145-MA/2009) and heterologous (A/Puerto Rico/8/1934) challenge with 10MLD50 mouse adapted virus. Although nanoparticle display conferred a small but statistically significant improvement in protection relative to the soluble trimer in a homologous challenge, heterologous protection was similar in both nanoparticle-stem immunized and trimeric stem immunized groups. Such rapidly producible, bacterially expressed antigens and nanoparticle scaffolds are useful modalities to tackle future influenza pandemics.

Dataset Information

Comparative analysis of the immunogenicity of monovalent and multivalent rotavirus immunogens.

Publications

Comparative analysis of the immunogenicity of monovalent and multivalent rotavirus immunogens.

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