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The Omicron variant of SARS-COV-2 (GISAID GRA clade [B.1.1.529, BA.1 and BA.2]) is now the single dominant Variant of Concern (VOC). The high number of mutations in the Omicron Spike (S) protein promotes humoral immunological escape. Although a third homologous boost with S, derived from the ancestral strain, was able to increase neutralizing antibody titers and breadth including to Omicron, the magnitude of virus neutralization could benefit from further optimization. Moreover, combining SARS-COV-2 strains as additional valences may address the current antigenicity range occupied by VOCs. Using Trimer-Tag platform we have previously demonstrated phase 3 efficacy and safety of a prototypic vaccine SCB-2019 in the SPECTRA trial and have submitted applications for licensure. Here, we successfully generated a bivalent vaccine candidate including both Ancestor and Omicron variant S-proteins. Preclinical studies demonstrate this SARS-CoV-2 bivalent S-Trimer subunit vaccine elicits high titers of neutralizing antibodies against all VOCs, with markedly enhanced Omicron specific neutralizing antibody responses.
RESUMEN
SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-levels of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.
RESUMEN
Objective@#To isolate the cariogenic Streptococcus mutans (Sm) strains and study the therapeutical effect of egg yolk antibody (IgY) of the Sm on dental caries development.@*Methods@#Sm strains were isolated from the children's dental plaque samples. Morphological, biochemical and molecular biological methods were applied to identify the serotype, acid producing and adhesion abilities of isolated Sm strains. After inactivation one of the Sm strains was used as antigen to immune laying hens to collect and extract the specific anti-Sm IgY. The rats were infected with Sm (serotype e). After 16 weeks of infection, all the rats were found developing dental caries. The rats were then randomly divided into two groups. The rats in experimental group were supplied with diet containing anti-Sm IgY while the rats in control group with normal IgY. All rats were sacrificed after another 8 weeks' observation. The degree of caries for each rat was assessed using Keyes' method.@*Results@#We isolated 7 Sm strains from the children's dental plaque samples in the present study. The numbers of serotype c, e, f, k were 3, 2, 0 and 2, respectively. All strains showed similar morphological and biochemical characters as standard UA159 Sm strain, and possessed strong capabilities of acid production and adherence. Interestingly, even the same serotypec strains, such as No.3 and No.7 strains, demonstrated significant difference on acid producing and adherence capabilities. After 16 weeks infection with serotype e strain, the rats' mandibular teeth were apparently decayed, and treatment with specific anti-Sm IgY obviously attenuated the development of caries in the experiment group rats (16.4±2.0) compared with that in the control group rats (30.2±9.3) (P<0.05) determined by Keyes' method.@*Conclusions@#Seven cariogenic Sm strains of different serotypes were isolated, which possesses similar morphology and biochemical characters. Although belonging to the same serotype strains they always show significant difference in acid-producing and adherencec apabilities. Further experiment provides evidences that the serotype e strain could obviously induce caries independently, and employment of specific anti-Sm IgY as passive immunotherapy additive might effectively inhibit the further development of dental caries.
RESUMEN
Objective To investigate the effects of Additive Foshousan(AFSS) on the serum levels of estradiol and progesterone in rats with primary dysmenorrhea. Methods SD rats were divided into six groups, each 10. Group 1 was normal control , groups 2,3 and 4 were treated with low, middle and high dose of AFSS(0.75, 1.5 and 3.0 g/kg) respectively, group 5 as positive controls was treated with Yuanhuzhitong tablets (1 mg/kg)and group 6 served as model control. Except the normal control group, all rats were injected diethylstilbestrol and oxytocin to establish primary dysmenorrhea model. The levels of estradiol(E2)and progesterone(P) in rats serum was determined by ELISA method and the ratio of E2/P was calculated. Results In middle and high dose of AFSS groups, the level of E2(48.27±6.42)pg/L,(47.51±7.03)pg/L respectively were lower than that in model group(54.47±9.12)pg/L and the difference was statistically significant(P<0.05). In low dose of AFSS group, the level of E2 was(50.83±6.26)pg/L and the difference was no statistically significant compared with model group. In all doses of AFSS groups,The content of P(687.41±21.14)ng/L, (720.47±41.03)ng/L, (719.78±32.01)ng/L respectively were higher than that in the model control group (667.32±46.51)ng/L and the difference was statistically significant(P<0.05 or<0.01). In middle and high dose of AFSS groups, the content of P were higher than that of Yuanhu-Zhitong tablets group(699.31±36.31)and the difference was statistically significant(P<0.05). Conclusion To reduce the content of E2, increase of P the content and decrease ratio of E2/P is one of the mechanism for AFSS to treat primary dysmenorrhea.
