Vaccination and Therapeutics.

In the wake of the novel Coronavirus, it has become imperative to develop vaccines that can alert our immune system to the virus, hence reducing the severity of disease if exposed to it. Different types of vaccines have been studied in this respect, such as nucleic acid vaccines (mRNA and DNA vaccines), vector-based vaccines, whole-virus vaccines (inactivated virus and live-attenuated vaccine), as well as protein subunits vaccines. The results have demonstrated that these vaccines are efficient against both the original strain and emerging variants. Furthermore, they also proved their safety with no grave adverse events. Despite this, hesitancy toward taking these vaccines is still present among certain groups in society due to various factors. Special emphasis has been placed on studies concerning pregnant women, children, elderly people, and immunocompromised individuals where efficacy and safety were proven.

A Comprehensive Analysis of COVID-19 Vaccine Discourse by Vaccine Brand on Twitter in Korea: Topic and Sentiment Analysis.

BACKGROUND: The unprecedented speed of COVID-19 vaccine development and approval has raised public concern about its safety. However, studies on public discourses and opinions on social media focusing on adverse events (AEs) related to COVID-19 vaccine are rare. OBJECTIVE: This study aimed to analyze Korean tweets about COVID-19 vaccines (Pfizer, Moderna, AstraZeneca, Janssen, and Novavax) after the vaccine rollout, explore the topics and sentiments of tweets regarding COVID-19 vaccines, and examine their changes over time. We also analyzed topics and sentiments focused on AEs related to vaccination using only tweets with terms about AEs. METHODS: We devised a sophisticated methodology consisting of 5 steps: keyword search on Twitter, data collection, data preprocessing, data analysis, and result visualization. We used the Twitter Representational State Transfer application programming interface for data collection. A total of 1,659,158 tweets were collected from February 1, 2021, to March 31, 2022. Finally, 165,984 data points were analyzed after excluding retweets, news, official announcements, advertisements, duplicates, and tweets with <2 words. We applied a variety of preprocessing techniques that are suitable for the Korean language. We ran a suite of analyses using various Python packages, such as latent Dirichlet allocation, hierarchical latent Dirichlet allocation, and sentiment analysis. RESULTS: The topics related to COVID-19 vaccines have a very large spectrum, including vaccine-related AEs, emotional reactions to vaccination, vaccine development and supply, and government vaccination policies. Among them, the top major topic was AEs related to COVID-19 vaccination. The AEs ranged from the adverse reactions listed in the safety profile (eg, myalgia, fever, fatigue, injection site pain, myocarditis or pericarditis, and thrombosis) to unlisted reactions (eg, irregular menstruation, changes in appetite and sleep, leukemia, and deaths). Our results showed a notable difference in the topics for each vaccine brand. The topics pertaining to the Pfizer vaccine mainly mentioned AEs. Negative public opinion has prevailed since the early stages of vaccination. In the sentiment analysis based on vaccine brand, the topics related to the Pfizer vaccine expressed the strongest negative sentiment. CONCLUSIONS: Considering the discrepancy between academic evidence and public opinions related to COVID-19 vaccination, the government should provide accurate information and education. Furthermore, our study suggests the need for management to correct the misinformation related to vaccine-related AEs, especially those affecting negative sentiments. This study provides valuable insights into the public discourses and opinions regarding COVID-19 vaccination.

COVID-19 vaccines in 2023.

Most Australian adults now have hybrid immunity to the SARS-CoV-2 virus, referring to a combination of protection from previous vaccine doses and past infection. Protection from both vaccination and past infection wanes over time. Booster doses are recommended to ensure that those who are at increased risk of severe COVID-19 remain protected. The optimal timing of future booster doses to maintain adequate protection against severe illness is not yet known. Older age remains the most important risk factor for severe COVID-19, including in the current Omicron variant era. The original COVID-19 vaccines are monovalent vaccines based on the ancestral strain of the SARS-CoV-2 virus. Bivalent vaccines have been developed based on earlier Omicron subvariants (BA.1 or BA.4-5) and the ancestral strain. These provide enhanced protection against severe illness from Omicron compared with the original monovalent vaccines. Updated monovalent vaccines based on a more recent Omicron subvariant (XBB.1.5) have been developed. COVID-19 vaccines have an excellent safety record, and serious adverse events are extremely rare.

A Case Report for Acute Myopericarditis After NVX-CoV2373 (Novavax®) COVID-19 Vaccination.

Post-vaccination myocarditis after administration of the NVX-CoV2373 coronavirus disease 2019 (COVID-19) vaccine has been reported in a limited population. We report the first biopsy-proven case of myopericarditis after administration of second dose of NVX-CoV2373 COVID-19 vaccine (Novavax®) in Korea. A 30-year-old man was referred to emergency department with complaints of chest pain and mild febrile sense for two days. He received the second dose vaccine 17 days ago. Acute myopericarditis by the vaccination was diagnosed by cardiac endomyocardial biopsy. He was treated with corticosteroid 1 mg/kg/day for 5 days and tapered for one week. He successfully recovered and was discharged on the 12th day of hospitalization. The present case suggests acute myopericarditis as a vaccination complication by Novavax® in Korea.

Short-Term Active Safety Surveillance of the Spikevax and Nuvaxovid Priming Doses in Australia.

Australia commenced administration of the Spikevax (Moderna mRNA-1273) COVID-19 vaccine in August 2021 and Nuvaxovid (Novavax NVX-CoV2373) in January 2022. This study describes the short-term safety profile of priming doses of the Spikevax and Nuvaxovid vaccines given between September 2021 and September 2023. Online surveys were sent via AusVaxSafety, Australia's active vaccine safety surveillance system, three and eight days after vaccination. A total of 131,775 day 3 surveys were sent, with a response rate of 38.5% (N = 50,721). A total of 43,875 day 8 surveys matched with day 3 survey responses were sent, with a response rate of 71.5% (N = 31,355). Half (50.7%) of respondents reported any adverse event following immunisation (AEFI) in the 0-3 days after vaccination and 24.6% reported any AEFI 4-7 days after vaccination. Fatigue, local pain, headache, and myalgia were the most frequently reported symptoms for both vaccines in both periods. After adjusting for respondent characteristics, vaccination clinic type, jurisdiction, and medical conditions, the odds for reporting AEFI increased with age from 16-19 years to highest odds at 30-39 years, after which it declined. Females had greater odd of reporting AEFI than males across most age groups, vaccine types, and doses. Respondents with a history of anaphylaxis had greater odds of reporting any AEFI (adjusted OR range: 1.50-2.86). A total of 3.1% of respondents reported seeking medical review 0-3 days after vaccination. This study affirms the short-term safety of Spikevax and Nuvaxovid COVID-19 vaccine priming doses in a large sample in Australia.

Dissecting human monoclonal antibody responses from mRNA- and protein-based XBB.1.5 COVID-19 monovalent vaccines.

The emergence of highly contagious and immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has required reformulation of coronavirus disease 2019 (COVID-19) vaccines to target those new variants specifically. While previous infections and booster vaccinations can enhance variant neutralization, it is unclear whether the monovalent version, administered using either mRNA or protein-based vaccine platforms, can elicit de novo B-cell responses specific for Omicron XBB.1.5 variants. Here, we dissected the genetic antibody repertoire of 603 individual plasmablasts derived from five individuals who received a monovalent XBB.1.5 vaccination either with mRNA (Moderna or Pfizer/BioNtech) or adjuvanted protein (Novavax). From these sequences, we expressed 100 human monoclonal antibodies and determined binding, affinity and protective potential against several SARS-CoV-2 variants, including JN.1. We then select two vaccine-induced XBB.1.5 mAbs, M2 and M39. M2 mAb was a de novo, antibody, i.e., specific for XBB.1.5 but not ancestral SARS-CoV-2. M39 bound and neutralized both XBB.1.5 and JN.1 strains. Our high-resolution cryo-electron microscopy (EM) structures of M2 and M39 in complex with the XBB.1.5 spike glycoprotein defined the epitopes engaged and revealed the molecular determinants for the mAbs' specificity. These data show, at the molecular level, that monovalent, variant-specific vaccines can elicit functional antibodies, and shed light on potential functional and genetic differences of mAbs induced by vaccinations with different vaccine platforms.\.

Safety and immunogenicity of a third dose of COVID-19 protein subunit vaccine (CovovaxTM) after homologous and heterologous two-dose regimens.

OBJECTIVES: To report the safety and immunogenicity profile of a protein subunit vaccine (CovovaxTM) given as a third (booster) dose to individuals primed with different primary vaccine regimens. METHODS: A third dose was administered to individuals with an interval range of 3-10 months after the second dose. The four groups were classified according to their primary vaccine regimens, including two-dose BBIBP-CorV, AZD1222, BNT162b2, and CoronaVac/AZD1222. Immunogenicity analysis was performed to determine binding antibodies, neutralizing activity, and the T-cell responses. RESULTS: Overall, 210 individuals were enrolled and boosted with the CovovaxTM vaccine. The reactogenicity was mild to moderate. Most participants elicited a high level of binding and neutralizing antibody against Wild-type and Omicron variants after the booster dose. In participants who were antinucleocapsid immunoglobulin G-negative from all groups, a booster dose could elicit neutralizing activity to Wild-type and Omicron variants by more than 95% and 70% inhibition at 28 days, respectively. The CovovaxTM vaccine could elicit a cell-mediated immune response. CONCLUSION: The protein subunit vaccine (CovovaxTM) can be proposed as a booster dose after two different priming dose regimens. It has strong immunogenicity and good safety profiles.

NVX-CoV2373 vaccine efficacy against hospitalization: A post hoc analysis of the PREVENT-19 phase 3, randomized, placebo-controlled trial.

PREVENT-19, the pivotal phase 3 trial of the Novavax adjuvanted, recombinant spike protein COVID-19 vaccine (NVX-CoV2373), demonstrated that the vaccine was well tolerated and efficacious (vaccine efficacy, VE = 90%) for the prevention of symptomatic COVID-19. In the trial, participants were randomly assigned in a 2:1 ratio to receive 2 doses of NVX-CoV2373 or placebo 21 days apart. Throughout the study, the predominant SARS-CoV-2 variant was alpha, but additional variants were in circulation (i.e., beta, gamma, epsilon, and iota). VE among the per-protocol efficacy analysis population was calculated according to pre-specified disease severity (mild, moderate, or severe) criteria, but the impact on the risk of COVID-19-associated hospitalization was not specifically investigated. During this analysis period (January 25, 2021, to April 30, 2021 [95 days]), 4 hospitalizations occurred among the 77 events analyzed for the primary endpoint using the per-protocol population, 0 among vaccine recipients and 4 among placebo recipients, yielding a post hoc VE against hospitalization of 100% (95% CI: 28.8, 100). Among an expanded efficacy population, also identified post hoc, which included COVID-19-associated hospitalizations without a requirement for diagnostic polymerase chain reaction testing performed at the study central laboratory, 12 total hospitalizations were identified, 0 among vaccine recipients and 12 among placebo recipients, yielding a post hoc VE against hospitalization of 100% (95% CI: 83.1, 100). These additional data from the PREVENT-19 trial provide relevant public health information concerning the attributes of NVX-CoV2373.

Safety of Four COVID-19 Vaccines across Primary Doses 1, 2, 3 and Booster: A Prospective Cohort Study of Australian Community Pharmacy Vaccinations.

Four COVID-19 vaccines are approved for use in Australia: Pfizer-BioNTech BNT162b2 (Comirnaty), AstraZeneca ChAdOx1 (Vaxzevria), Moderna mRNA-1273 (Spikevax) and Novavax NVX-CoV2373 (Nuvaxovid). We sought to examine adverse events following immunisation (AEFI) at days 3 and 42 after primary doses 1, 2, 3 and booster. We conducted active vaccine safety surveillance from 130 community pharmacies in Australia integrated with AusVaxSafety, between August 2021-April 2022. Main outcomes: AEFI at 0-3 days post-vaccination; medical review/advice at 3 days and 42 days post-vaccination; SARS-CoV-2 breakthrough infection by day 42. Of 110,024 completed day 3 surveys (43.6% response rate), 50,367 (45.8%) reported any AEFI (highest proportions: Pfizer 42%, primary dose 3; AstraZeneca 58.3%, primary dose 1; Moderna 65.4% and Novavax 58.8%, both primary dose 2). The most common AEFI reported across all doses/vaccines were local reactions, systemic aches and fatigue/tiredness. Overall, 2172/110,024 (2.0%) and 1182/55,329 (2.1%) respondents sought medical review at days 3 and 42, respectively, and 931/42,318 (2.2%) reported breakthrough SARS-CoV-2 infection at day 42. We identified similar AEFI profiles but at lower proportions than previously reported for Pfizer, AstraZeneca, Moderna and Novavax COVID-19 vaccines. Moderna vaccine was the most reactogenic and associated with higher AEFI proportions across primary doses 2, 3, and booster.

An Immunological Review of SARS-CoV-2 Infection and Vaccine Serology: Innate and Adaptive Responses to mRNA, Adenovirus, Inactivated and Protein Subunit Vaccines.

The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, which is defined by its positive-sense single-stranded RNA (ssRNA) structure. It is in the order Nidovirales, suborder Coronaviridae, genus Betacoronavirus, and sub-genus Sarbecovirus (lineage B), together with two bat-derived strains with a 96% genomic homology with other bat coronaviruses (BatCoVand RaTG13). Thus far, two Alphacoronavirus strains, HCoV-229E and HCoV-NL63, along with five Betacoronaviruses, HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2, have been recognized as human coronaviruses (HCoVs). SARS-CoV-2 has resulted in more than six million deaths worldwide since late 2019. The appearance of this novel virus is defined by its high and variable transmission rate (RT) and coexisting asymptomatic and symptomatic propagation within and across animal populations, which has a longer-lasting impact. Most current therapeutic methods aim to reduce the severity of COVID-19 hospitalization and virus symptoms, preventing the infection from progressing from acute to chronic in vulnerable populations. Now, pharmacological interventions including vaccines and others exist, with research ongoing. The only ethical approach to developing herd immunity is to develop and provide vaccines and therapeutics that can potentially improve on the innate and adaptive system responses at the same time. Therefore, several vaccines have been developed to provide acquired immunity to SARS-CoV-2 induced COVID-19-disease. The initial evaluations of the COVID-19 vaccines began in around 2020, followed by clinical trials carried out during the pandemic with ongoing population adverse effect monitoring by respective regulatory agencies. Therefore, durability and immunity provided by current vaccines requires further characterization with more extensive available data, as is presented in this paper. When utilized globally, these vaccines may create an unidentified pattern of antibody responses or memory B and T cell responses that need to be further researched, some of which can now be compared within laboratory and population studies here. Several COVID-19 vaccine immunogens have been presented in clinical trials to assess their safety and efficacy, inducing cellular antibody production through cellular B and T cell interactions that protect against infection. This response is defined by virus-specific antibodies (anti-N or anti-S antibodies), with B and T cell characterization undergoing extensive research. In this article, we review four types of contemporary COVID-19 vaccines, comparing their antibody profiles and cellular aspects involved in coronavirus immunology across several population studies.

SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines.

All current vaccines for COVID-19 utilize ancestral SARS-CoV-2 spike with the goal of generating protective neutralizing antibodies. The recent emergence and rapid spread of several SARS-CoV-2 variants carrying multiple spike mutations raise concerns about possible immune escape. One variant, first identified in the United Kingdom (B.1.1.7, also called 20I/501Y.V1), contains eight spike mutations with potential to impact antibody therapy, vaccine efficacy, and risk of reinfection. Here, we show that B.1.1.7 remains sensitive to neutralization, albeit at moderately reduced levels (∼sim;2-fold), by serum samples from convalescent individuals and recipients of an mRNA vaccine (mRNA-1273, Moderna) and a protein nanoparticle vaccine (NVX-CoV2373, Novavax). A subset of monoclonal antibodies to the receptor binding domain (RBD) of spike are less effective against the variant, while others are largely unaffected. These findings indicate that variant B.1.1.7 is unlikely to be a major concern for current vaccines or for an increased risk of reinfection.

A review on the advancements in the development of vaccines to combat coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19), the deadly disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a global pandemic that has severely affected lives and economies around the globe. The spread of this virus will be very difficult to contain if no vaccine is ready for implementation. This is because of the high human-to-human transmission rate of this virus and the fact that the virus is in the community spread stage. As of 31st August 2020, 25.3 million individuals have been affected by this deadly virus resulting in about 850,673 deaths. To combat the spread of COVID-19, more than 100 applicant immunizations are being developed around the world. Among them, eight have begun or will be soon beginning preliminary clinical trials. This paper provides a review of the current developments of potential COVID-19 vaccines around the world. It specifically discusses the recombinant vaccine produced by the University of Oxford and AstraZeneca (Cambridge, UK), the use of novel self-amplifying RNA technique to create a vaccine and the progress made by UNAID (US National Institute of Allergy and Infectious Diseases) and World Health Organization (WHO). Furthermore, this review demonstrates the pharmaceutical prophylaxis and treatment protocols for COVID-19 by analysing the documentation set up by the WHO for up to date data with respect to the novel coronavirus of 2019-2020.