ABSTRACT
Clinically licensed COVID-19 vaccines ameliorate viral infection by inducing vaccinee production of neutralizing antibodies that bind to the SARS-CoV-2 Spike protein to inhibit viral cellular entry (Walsh et al., 2020; Baden et al., 2021), however the clinical effectiveness of these vaccines is transitory as viral variants arise that escape antibody neutralization (Tregoning et al., 2021; Willett et al., 2022). Vaccines that solely rely upon a T cell response to combat viral infection could be transformational because they can be based on highly conserved short peptide epitopes that hold the potential for pan-variant immunity, but a mRNA-LNP T cell vaccine has not been shown to be sufficient for effective antiviral prophylaxis. Here we show that a mRNA-LNP vaccine based on highly conserved short peptide epitopes activates a CD8+ and CD4+ T cell response that prevents mortality in HLA-A*02:01 transgenic mice infected with the SARS-CoV-2 Beta variant of concern (B.1.351). In mice vaccinated with the T cell vaccine, 24% of the nucleated cells in lung were CD8+ T cells on day 7 post infection. This was 5.5 times more CD8+ T cell infiltration of the lungs in response to infection compared to the Pfizer-BioNTech Comirnaty(R) vaccine. Between days 2 and 7 post infection, the number of CD8+ T cells in the lung increased in mice vaccinated with the T cell vaccine and decreased in mice vaccinated with Comirnaty(R). The T cell vaccine did not produce neutralizing antibodies, and thus our results demonstrate that SARS-CoV-2 viral infection can be controlled by a T cell response alone. Our results suggest that further study is merited for pan-variant T cell vaccines, and that T cell vaccines may be relevant for individuals that cannot produce neutralizing antibodies or to help mitigate Long COVID.
ABSTRACT
Emergence of SARS-CoV-2 variants of concern (VOC), including the highly transmissible delta strain, has posed challenges to current COVID-19 vaccines that principally target the viral spike protein (S). Here, we report a nucleoside-modified mRNA vaccine that expresses the more conserved viral nucleoprotein (mRNA-N). We show that mRNA-N alone was able to induce a modest but significant control of SARS-CoV-2 in mice and hamsters. Critically, by combining mRNA-N with the clinically approved S-expressing mRNA vaccine (mRNA-S-2P), we found that combinatorial mRNA vaccination (mRNA-S+N) led to markedly enhanced protection against the SARS-CoV-2 delta variant compared to mRNA-S. In a hamster model, we demonstrated that while mRNA-S alone elicited significant control of the delta strain in the lungs ([~]45-fold reduction in viral loads compared to un-vaccinated control), its effectiveness in the upper respiratory tract was weak, whereas combinatorial mRNA-S+N vaccination induced markedly more robust control of the delta variant infection in the lungs ([~]450-fold reduction) as well as in the upper respiratory tract ([~]20-fold reduction). Immune analyses indicated that induction of N-specific immunity as well as augmented S-specific T-cell response and neutralizing antibody activity were collectively associated the enhanced protection against SARS-CoV-2 delta strain by combinatorial mRNA vaccination. These findings suggest that the combined effects of protection in the lungs and upper respiratory tract could both reduce the risk of severe disease as well as of infection and transmission.
ABSTRACT
Objective To study the antibiotic resistance of Neisseria gonorrhoeae and the prevalence of penicillinase-producing Neisseria gonorrhoeae (PPNG) and high-level tetracycline resistant Neisseria gonorrhoeae (TRNG) in Nanning. Methods Minimum inhibitory concentrations (MIC) were determined by agar dilution method and ?-lactamase production was comfirmed by acidometric method.Results Among 458 strains, 33 strains(7.20%) were found to be PPNG and 231 strains(50.44%) were TRNG. The resistance rate to ciprofloxacin, ceftriaxone and spectinomycin were 87.33%, 1.31% and 0.22% respectively. Conclusion The situation of resistance to ciprofloxacin was very serious, and it was also found that a few of gonococcal isolates were resistant to ceftriaxone and spectinomycin. The study showed that it is important to successively survey the antibiotic resistance of Neisseria gonorrhoeae.
ABSTRACT
Objective To understand the changes of NKT cells in the livers and spleens of mice infected with Schistosoma japonicum.Methods Twenty-four female BALB/c mice aged 6-8 weeks were randomly divided into 4 groups.Three groups of mice were infected with(14?2)cercariae of S.japonicum.In 3,6 and 12 weeks post-infection,the mice were randomly chosen from each group and sacrificed resectively and the lymphocytes were harvested from the livers and spleens.The cells were stained with fluorescein-isothiocyanate(FITC)-conjugated anti-mouse pan-NK cells(CD49b)and phycoerythrin(PE)anti-mouse CD3e monoclonal antibodies,respectively.The proportion of NKT cells was analyzed by flow cytometry.In the experiment in vitro,the lymphocytes from spleens of normal mice were harvested and stimulated with SEA,the protein constituents of eggs and lipid constituents of eggs,respectively.The proportion of NKT cells was also analyzed by flow cytometry.Results The proprotion of splenic NKT cells in lymphocytes in 12 weeks post-infection was(4.73?0.41)%,which was significantly higher than that of the control(2.07?0.12)%(P
ABSTRACT
Objective To identify the possible existing suppressive oligodeoxynucleotides(ODNs)in the DNA sequence which encodes Schistosoma japonicum 22.6 kDa(Sj22.6)antigen.Methods Several ODNs within the DNA sequence encoding Sj22.6 antigen were synthesized.Splenocytes separated from mice were stimulated with optimal immunostimulatory CpG 1826 in the absence or presence of different synthetical ODNs.The suppressive efficacy of each ODN was examined by 3H-TdR incorporation.Results ODN F311 suppressed the proliferation of splenocytes caused by CpG 1826 stimulation.The significant suppression was observed when ODN F311∶CpG 1826 at a ratio of 1∶1 and 3∶1,the suppression reached 11% and 58% respectively.The maximal inhibition was observed when ODN F311 was pre-administered with CpG ODN for 2 h.Conclusions Certain suppressive ODN exists in the DNA sequence encoding Sj22.6 antigen,and this effect shows dose-and time-dependent manner.
