ABSTRACT
An unequitable vaccine allocation and continuously emerging SARS-CoV-2 variants pose challenges to contain the pandemic, which underscores the need for licensing more vaccine candidates, increasing manufacturing capacity and implementing better immunization strategy. Here, we report data from a proof-of-concept investigation in two healthy individuals who received two doses of inactivated whole-virus COVID-19 vaccines, followed by a single heterologous boost vaccination after 7 months with an mRNA vaccine candidate (LPP-Spike-mRNA) developed by Stemirna Therapeutics. Following the boost, Spike-specific antibody (Ab), memory B cell and T cell responses were significantly increased. These findings indicate that a heterologous immunization strategy combining inactivated and mRNA vaccines can generate robust vaccine responses and therefore provide a rational and effective vaccination regimen.
ABSTRACT
BACKGROUNDIn-depth investigations of the safety and immunogenicity of inactivated SARS-CoV-2 vaccines are needed. METHODIn a phase I randomized, double-blinded, and placebo-controlled trial involving 192 healthy adults 18-59 years of age, two injections of three different doses (50 EU, 100 EU and 150 EU) of an inactivated SARS-CoV-2 vaccine or the placebo were administered intramuscularly with a 2- or 4-week interval between the injections. The safety and immunogenicity of the vaccine were evaluated within 28 days. FINDINGIn this study, 191 subjects assigned to three doses groups or the placebo group completed the 28-day trial. There were 44 adverse reactions within the 28 days, most commonly mild pain and redness at the injection site or slight fatigue, and no abnormal variations were observed in 48 cytokines in the serum samples of immunized subjects. The serum samples diluted from 1:32 to 1:4096 and incubated with the virus did not show antibody-dependent enhancement effects (ADEs) with regard to human natural killer cells, macrophages or dendritic cells. At day 14, the seroconversion rates had reached 92%, 100% and 96% with geometric mean titers (GMTs) of 18.0, 54.5 and 37.1, and at day 28, the seroconversion rates had reached 80%, 96% and 92% with GMTs of 10.6, 15.4 and 19.6in 0, 14 and 0, 28 procedures, respectively. Seroconversion was associated with the synchronous upregulation of ELISA antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. Transcriptome analysis shaped the genetic diversity of immune response induced by the vaccine. INTERPRETATIONIn a population aged 18-59 years, this inactivated SARS-CoV-2 vaccine was safe and immunogenic. Trial registrationNCT04412538 FUNDINGThe National Key R&D Program of China (2020YFC0849700), the Program of Chinese Academy of Medicine Science and the Major Science and Technology Special Projects of Yunnan Province.
ABSTRACT
Objective To investigate the dynamic changes of three types of anti-poliovirus neutralizing antibodies and anti-hepatitis A virus (HAV) IgG antibody in children who were immunized with inactivated enterovirus 71 (EV71) vaccine (human diploid cell).Methods Serum samples were collected from the subjects immunized with inactivated EV71 vaccine.Neutralizing antibodies against EV71 and poliovirus were detected by micro-cytopathic effect neutralization test.Enzyme linked immunosorbent assay (ELISA) was used to detect IgG antibody against HAV.Results The geometric mean titers (GMTs) of anti-EV71 neutralizing antibody increased to 4.85 following the first-dose injection of inactivated EV71 vaccine.A significant increase of GMTs (up to 64.37) could be observed 28 days after the second-dose vaccination.Meanwhile, results of the dynamic monitor showed that there were slight fluctuations in the neutralizing antibodies against three types of poliovirus on day 28 (28 days after the first-dose vaccination) compared with those on day 0 (before vaccination) (P0.05).The level of anti-HAV IgG antibody was stable and no significant difference was found during the observation period (P>0.05).Conclusion This study shows that inactivated EV71 vaccine has no impact on anti-HAV IgG antibody in Children during the two-dose vaccination and in anti-EV71 antibody-producing period, but has slight influence on the anti-poliovirus antibodies.In general, changes in antibody profile do not affect the clinical efficacy of immune response.
ABSTRACT
The comparative analysis of the biological characterization and the genetic background study of EV71 circulating strains is commonly recognized as basic work necessary for development of an effective EV71 vaccine. In this study, we sequenced five EV71 circulating strains, isolated from Fuyang, Hefei, Kunming and Shenzhen city of China and named them FY-23, FY-22, H44, K9 and S1 respectively. The sequence alignment demonstrated their genotypes be C4. The genetic distance of the VP1 gene from these isolates suggested that they were highly co-related with genetic identity similar to other previously reported EV71 strains in China. Additionally, these strains were identified to display some obvious proliferation dynamics and plaque morphology when propagated in Vero cells. However, a distinctive difference in pathogenic ability in neonatal mice was found. Some differences in cross neutralization test & immunogenic analysis were also found. All these results are related to the biological characterization of circulating EV71 strains in China and aid in the development of an EV71 vaccine in the future.
