New onset rheumatoid arthritis with refractory hyper-eosinophilia associated with inactivated COVID-19 vaccine

COVID-19 vaccines are considered one of the primary strategies for countering the pandemic. While mRNA based and viral vector-based vaccines have been predominantly used, inactivated SARS-CoV-2 vaccines are being manufactured in countries such as China and India. Post approval, rare but serious adverse events such as myocarditis and stroke have been observed with mRNA based and viral vectored COVID-19 vaccines. Inactivated vaccines in general have shown better tolerability in clinical trials. Here we report the first case of new-onset seropositive rheumatoid arthritis (RA) with rheumatoid nodules and refractory reactive eosinophilia within two weeks of receiving an inactivated COVID-19 vaccine (COVAXIN).

Nucleic Acid-Based Vaccines Platform Against Covid-19 Pandemic

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected millions of people globally, in this regard, known as a pandemic by the World Health Organization (WHO). There is sufficient scientific evidence that a preventive COVID-19 vaccine is the most effective approach to combat with COVID-19 pandemic, therefore there is an essential need for safe and protective vaccines to fight it. Methods: Global efforts in developing a vaccine against COVID-19 have resulted in the development of different vaccine platforms with various safety and efficacy including live-attenuated vaccines, inactivated vaccines, subunit vaccines, and nucleic acid-based vaccines against coronavirus disease 2019 (COVID-19). Nucleic acid-based vaccines consist of mRNA and DNA vaccines have shown promising results in stimulating cellular and humoral immune responses properly against COVID-19, which their rapid and easy manufacturing process compared to others have made them considerable. mRNA-based vaccines platform by Pfizer/BioNtech and Moderna companies are the first approved vaccines for emergency use against COVID-19. Results: This narrative review highlights the recent advances in developing nucleic acid-based vaccines for COVID-19. Conclusion: The fast global dissemination of the coronavirus has highlighted the urgent necessity to build an efficient vaccine to inhibit disease. Cooperative attempts throughout the world have paid to the fast and unprecedented production of vaccines. Much needs to be learned regarding SARSCoV-2 and vaccine development against it.

Heterologous vaccination with inactivated and mRNA vaccines increases B and T cell responses to SARS-CoV-2

Background There has been an unprecedented global effort to produce safe and effective vaccines against SARS-CoV-2. However, production challenges, supply shortages and unequal global reach, together with an increased number of breakthrough infections due to waning of immunity and the emergence of new variants of concern (VOC), have prolonged the pandemic. To boost the immune response, several heterologous vaccination regimes have been tested and have shown increased antibody responses compared to homologous vaccination. Here we evaluated the effect of mRNA vaccine booster on immunogenicity in individuals who had been vaccinated with two doses of inactivated vaccines. Methods The levels of specific antibodies against the receptor-binding domain (RBD) of the spike protein from wild-type virus and the Beta, Delta and Omicron variants were measured in healthy individuals who had received two doses of homologous inactivated (BBIBP-CorV or CoronoVac) or mRNA (BNT162b2 or mRNA-1273) vaccines, and in donors who were given an mRNA vaccine boost after two doses of either vaccine. Pre-vaccinated healthy donors, or individuals who had been infected and subsequently received the mRNA vaccine were also included as controls. In addition, specific memory B and T cell responses were measured in a subset of samples. Results A booster dose of an mRNA vaccine significantly increased the specific antibody response to the wild-type and VOCs including Omicron (by 14-fold), in individuals who had previously received two doses of inactivated vaccines. The levels of specific antibodies in the heterologous vaccination group were similar to those in individuals receiving a third dose of homologous mRNA vaccines or boosted with mRNA vaccine after natural infection. Furthermore, this heterologous vaccination regime significantly improved the specific memory B and T cell responses. Conclusions Heterologous prime-boost immunization with inactivated vaccine followed by an mRNA vaccine boost markedly increased the levels of specific antibodies and B and T cell responses and may thus increase protection against emerging SARS-CoV-2 variants including Omicron.

Sequential immunization with SARS-CoV-2 RBD vaccine induces potent and broad neutralization against variants in mice

The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.

How to Increase the Immunogenicity of SARS-COV-2 Inactivated Vaccines?

The article's abstract is not available.

Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells

Inactivated vaccines based on cell culture are very useful in the prevention and control of many diseases. The most popular strategy for the production of inactivated vaccines is based on monkey-derived Vero cells, which results in high productivity of the virus but has a certain carcinogenic risk due to non-human DNA contamination. Since human diploid cells, such as MRC-5 cells, can produce a safer vaccine, efforts to develop a strategy for inactivated vaccine production using these cells have been investigated using MRC-5 cells. However, most viruses do not replicate efficiently in MRC-5 cells. In this study, we found that rabies virus (RABV) infection activated a robust interferon (IFN)-β response in MRC-5 cells but almost none in Vero cells, suggesting that the IFN response could be a key limiting factor for virus production. Treatment of the MRC-5 cells with IFN inhibitors increased RABV titers by 10-fold. Additionally, the RABV titer yield was improved five-fold when using IFN receptor 1 (IFNAR1) antibodies. As such, we established a stable IFNAR1-deficient MRC-5 cell line (MRC-5IFNAR1−), which increased RABV production by 6.5-fold compared to normal MRC-5 cells. Furthermore, in a pilot-scale production in 1500 square centimeter spinner flasks, utilization of the MRC-5IFNAR1− cell line or the addition of IFN inhibitors to MRC cells increased RABV production by 10-fold or four-fold, respectively. Thus, we successfully established a human diploid cell-based pilot scale virus production platform via inhibition of IFN response for rabies vaccines, which could also be used for other inactivated virus vaccine production.

Efficacy of the Newcastle Disease Virus Genotype VII.1.1-Matched Vaccines in Commercial Broilers

Class II genotype VII Newcastle disease viruses (NDV) are predominant in the Middle East and Asia despite intensive vaccination programs using conventional live and inactivated NDV vaccines. In this study, the protective efficacies of three commercial vaccine regimes involving genotype II NDV, recombinant genotype VII NDV-matched, and an autogenous velogenic NDV genotype VII vaccine were evaluated against challenge with velogenic NDV genotype VII (accession number MG029120). Three vaccination regimes were applied as follows: group-1 received inactivated genotype II, group-2 received inactivated recombinant genotype VII NDV-matched, and group-3 received velogenic inactivated autogenous NDV genotype VII vaccines given on day 7; for the live vaccine doses, each group received the same live genotype II vaccine. The birds in all of the groups were challenged with NDV genotype VII, which was applied on day 28. Protection by the three regimes was evaluated after infection based on mortality rate, clinical signs, gross lesions, virus shedding, seroconversion, and microscopic changes. The results showed that these three vaccination regimes partially protected commercial broilers (73%, 86%, 97%, respectively, vs. 8.6% in non-vaccinated challenged and 0% in non-vaccinated non-challenged birds) against mortality at 10 days post-challenge (dpc). Using inactivated vaccines significantly reduced the virus shedding at the level of the number of shedders and the amount of virus that was shed in all vaccinated groups (G1-3) compared to in the non-vaccinated group (G-4). In conclusion, using closely genotype-matched vaccines (NDV-GVII) provided higher protection than using vaccines that were not closely genotype-matched and non-genotype-matched. The vaccine seeds that were closely related to genotype VII.1.1 provided higher protection against challenge against this genotype since it circulates in the Middle East region. Updating vaccine seeds with recent and closely related isolates provides higher protection.

Waning immune responses against SARS-CoV-2 among vaccinees in Hong Kong

Background: Nearly 4 billion doses of the BioNTech-mRNA and Sinovac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated. Methods: We compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people. Findings: Standard BioNTech and Sinovac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC 50 and median frequencies of reactive CD4 subsets were consistently lower among Sinovacvaccinees than BioNTech-vaccinees. Against VOCs, NAb response rate and geometric mean IC 50 against B1.351 and B.1.617.2 were significantly lower for Sinovac (14.3%, 15 and 50%, 23.2) than BioNTech (79.4%, 107 and 94.1%, 131). Three months after vaccinations, NAbs to VOCs dropped near to detection limit, along with waning memory T cell responses, mainly among Sinovac-vaccinees. Interpretation: Our results indicate that Sinovac-vaccinees may face higher risk to pandemic VOCs breakthrough infection.