Assessment of S-Specific IgG and IgM Positive Rates in Healthy Hospital Staff Members Vaccinated with the Inactivated SARS-CoV-2 Vaccine.

Widespread vaccination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine makes the assessment of antibodies' positive rates essential. In this study, a total of 378 hospital staff members vaccinated with the vaccine were selected as research subjects. Serum-specific IgG and IgM against the SARS-CoV-2 spike protein (S) were detected, and S-specific IgG and IgM positive rates were analyzed in different age and sex groups, as was the serological pattern of IgG/IgM. The positive rates of IgG and IgM were 92.06% and 44.44%, respectively. The percentage of both IgG and IgM positive (IgG+IgM+) was 43.92%. A total of 182 vaccinees (46.90%) were IgG positive and IgM negative (IgG+IgM-), and 28 vaccinees (7.41%) were negative for both IgG and IgM (IgG-IgM-); 2 participants were positive for IgM alone (IgG-IgM+). In sex subgroups, the rate of IgM positivity was significantly higher in the male group than in the female group (p = 0.027). In different age subgroups, positive rates for IgG in the young group were significantly higher than those in the other group (p = 0.035). Furthermore, ratios of sample values to cutoff values (S/CO values) for IgG in vaccinees who were S-specific IgG positive were compared, and the S/CO values of IgG were significantly higher in the younger group than in the other group (p < 0.001). When comparing the influence of sex on two specific serological patterns (IgG+IgM- and IgG+IgM+), a significant difference in positivity rates was detected (p = 0.011). Male vaccinees were more likely than females to have an IgG+IgM+ pattern.

Characterization of an Escherichia coli-derived human papillomavirus type 16 and 18 bivalent vaccine.

Human papillomavirus (HPV) types 16 and 18 account for approximately 70% of cervical cancer worldwide. Neutralizing HPV prophylactic vaccines offer significant benefit, as they block HPV infection and prevent subsequent disease. However, the three licensed HPV vaccines that cover these two genotypes were produced in eukaryotic cells, which is expensive, particularly for low-income countries where HPV is highest. Here, we report a new HPV16 and -18 bivalent candidate vaccine produced from Escherichia coli. We used two strategies of N-terminal truncation of HPV L1 proteins and soluble non-fusion expression to generate HPV16 and HPV18 L1-only virus-like particles (VLPs) in a scalable process. Through comprehensive characterization of the bivalent candidate vaccine, we confirm lot consistency in a pilot scale-up of 30L, 100L and 500L. Using cryo-EM 3D reconstruction, we found that HPV16 and -18VLPs present in a T=7 icosahedral arrangement, similar in shape and size to that of the native virions. This HPV16/18 bivalent vaccine shares comparable immunogenicity with the licensed vaccines. Overall, we show that the production of a HPV16/18 bivalent vaccine from an E. coli expression system is robust and scalable, with potentially good accessibility worldwide as a population-based immunization strategy.

Bacterially expressed human papillomavirus type 6 and 11 bivalent vaccine: Characterization, antigenicity and immunogenicity.

Human papillomavirus (HPV)-6 and HPV11 are the major etiological causes of condylomata acuminate. HPV neutralization by vaccine-elicited neutralizing antibodies can block viral infection and prevent subsequent disease. Currently, two commercially available HPV vaccines cover these two genotypes, expressed by Saccharomyces cerevisiae. Here we describe another HPV6/11 bivalent vaccine candidate derived from Escherichia coli. The soluble expression of N-terminally truncated L1 proteins was optimized to generate HPV6- and HPV11 L1-only virus-like particles (VLPs) as a scalable process. In a pilot scale, we used various biochemical, biophysical and immunochemical approaches to comprehensively characterize the scale and lot consistency of the vaccine candidate at 30L and 100L. Cryo-EM structure analysis showed that these VLPs form a T=7 icosahedral lattice, imitating the L1 capsid of the authentic HPV virion. This HPV6/11 bivalent vaccine confers a neutralization titer and antibody production profile in monkey that is comparable with the quadrivalent vaccine, Gardasil. This study demonstrates the robustness and scalability of a potential HPV6/11 bivalent vaccine using a prokaryotic system for vaccine production.

Functional assessment and structural basis of antibody binding to human papillomavirus capsid.

Persistent high-risk human papillomavirus (HPV) infection is linked to cervical cancer. Two prophylactic virus-like particle (VLP)-based vaccines have been marketed globally for nearly a decade. Here, we review the HPV pseudovirion (PsV)-based assays for the functional assessment of the HPV neutralizing antibodies and the structural basis for these clinically relevant epitopes. The PsV-based neutralization assay was developed to evaluate the efficacy of neutralization antibodies in sera elicited by vaccination or natural infection or to assess the functional characteristics of monoclonal antibodies. Different antibody binding modes were observed when an antibody was complexed with virions, PsVs or VLPs. The neutralizing epitopes are localized on surface loops of the L1 capsid protein, at various locations on the capsomere. Different neutralization antibodies exert their neutralizing function via different mechanisms. Some antibodies neutralize the virions by inducing conformational changes in the viral capsid, which can result in concealing the binding site for a cellular receptor like 1A1D-2 against dengue virus, or inducing premature genome release like E18 against enterovirus 71. Higher-resolution details on the epitope composition of HPV neutralizing antibodies would shed light on the structural basis of the highly efficacious vaccines and aid the design of next generation vaccines. In-depth understanding of epitope composition would ensure the development of function-indicating assays for the comparability exercise to support process improvement or process scale up. Elucidation of the structural elements of the type-specific epitopes would enable rational design of cross-type neutralization via epitope re-engineering or epitope grafting in hybrid VLPs.