Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease in infants and children with potential for fatal complications such as encephalitis and acute flaccid myelitis. This study examined the long-term immunity conferred by EV71vac, an inactivated EV-A71 vaccine adjuvanted with aluminum phosphate, in children from the age of 2 months to <6 years, for up to 5 years after the first immunization. A total of 227 participants between 2 months and <6 years of age who had previously received either EV71vac or placebo in the phase two clinical study were enrolled. Subjects were divided into age groups: 2 years to <6 years (Group 2b), 6 months to <2 years (Group 2c), and 2 months to <6 months (Group 2d). At Year 5, the neutralizing antibody titers against the B4 subgenotype remained high at 621.38 to 978.20, 841.40 to 1159.93, and 477.71 to 745.07 for Groups 2b, 2c, and 2d, respectively. Cross-neutralizing titers at Year 5 remained high against B5 and C4a subgenotypes, respectively. No long-term safety issues were reported. Our study provides novel insights into the long-term immunity conferred by EV71vac in children aged from two months to six years, particularly in those who received EV71vac between two and six months of age.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 is a worldwide health emergency. The immense damage done to public health and economies has prompted a global race for cures and vaccines. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein by adding two proline substitutions at the top of the central helix (S-2P). To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P was combined with various adjuvants, including CpG 1018, and administered to mice to test its effectiveness in eliciting anti-SARS-CoV-2 neutralizing antibodies. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of spike-specific antibodies in sera of immunized mice. The neutralizing abilities in pseudotyped lentivirus reporter or live wild-type SARS-CoV-2 were measured with reciprocal inhibiting dilution (ID ₅₀ ) titers of 5120 and 2560, respectively. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th-1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens with up to 50 μg of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018/alum as a candidate vaccine to prevent COVID-19 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines based on variant strains have been in use as booster doses to update immunity against circulating variants. Here we present the results of a phase one prospective, randomized, and open-labeled trial to study the safety and immunogenicity of a booster dose consisting of a subunit vaccine based on the stabilized prefusion SARS-CoV-2 spike protein, MVC-COV1901, or its Beta version, MVC-COV1901-Beta. Participants aged ≥18 and <55 years who received two or three prior doses of MVC-COV1901 vaccines were enrolled and were to receive a booster dose of either 15 mcg of MVC-COV1901, 15 mcg, or 25 mcg of MVC-COV1901-Beta in a 1:1:1 ratio. Adverse reactions after either MVC-COV1901 or MVC-COV1901-Beta booster doses after two or three doses of MVC-COV1901 were comparable and mostly mild and transient. At four weeks after the booster dose, participants with two prior doses of MVC-COV1901 had higher levels of neutralizing antibodies against ancestral SARS-CoV-2, Beta, and Omicron variants than participants with three prior doses of MVC-COV1901, regardless of the type of booster used. MVC-COV1901 and MVC-COV1901-Beta can both be effectively used as booster doses against SARS-CoV-2, including the BA.4/BA.5 Omicron variants.

: Background: EV-A71 causes hand, foot, and mouth disease with potentially fatal complications such as encephalitis and acue flaccid myelitis in infants and children. This study examined the long-term immunity conferred by EV71vac, an inactivated EV-A71 vaccine based on the B4 subgenotype adjuvanted with aluminum phosphate, in children from the age of > 2 months to < 6 years for up to 5 years after the first immunization. Methods: A total of 227 subjects from age of 2 months to 6 years who had previously received either EV71vac or placebo in the phase 2 clinical study were enrolled. Subjects were split into age groups: 2 years to < 6 years (Group 2b), 6 months to < 2 years (Group 2c), and 2 months to < 6 months (Group 2d). Serum samples were taken periodically for up to five years after the first dose for immunogenicity against EV-A71. Results: At year 5, the neutralizing antibody titers against B4 subgenotype remained high at 621.38 to 978.20, 841.40 to 1159.93, and 477.71 to 745.07 for Groups 2b, 2c, and 2d, respectively. Cross-neutralizing titers at year 5 were 99.14 to 444.30 and 341.94 to 998.20 against B5 and C4a subgenotypes, respectively. Nearly all subjects remained seroprotected at year five (95.8 to 100%). No long-term safety issues were reported. Conclusion: This study shows that using the current dosing regimen, EV71vac conferred persistent immunity against EV-A71 for at least five years after the first vaccination in children from the age of two months to six years. Summary: EV-A71 neutralizing antibody persisted at high level throughout five years post vaccination in children of two months to six years old.