Evaluation of Vaccine Efficacy, Safety and Immunogenicity against Influenza and COVID-19

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a very rare but serious adverse reaction that can occur after Ad26.COV2.S vaccination in humans, leading to thrombosis at unusual anatomic sites. One hypothesis is that accidental intravenous (IV) administration of Ad26.COV2.S or drainage of the vaccine from the muscle into the circulatory system may result in interaction of the vaccine with blood factors associated with platelet activation, leading to VITT. Here, we demonstrate that, similar to intramuscular (IM) administration of Ad26.COV2.S in rabbits, IV dosing was well tolerated, with no significant differences between dosing routes for the assessed hematologic, coagulation time, innate immune, or clinical chemistry parameters and no histopathologic indication of thrombotic events. For both routes, all other non-adverse findings observed were consistent with a normal vaccine response and comparable to those observed for unrelated or other Ad26-based control vaccines. However, Ad26.COV2.S induced significantly higher levels of C-reactive protein on day 1 after IM vaccination compared with an Ad26-based control vaccine encoding a different transgene, suggesting an inflammatory effect of the vaccine-encoded spike protein. Although based on a limited number of animals, these data indicate that an accidental IV injection of Ad26.COV2.S may not represent an increased risk for VITT. Full article

Background: Immune response to SARS-CoV-2 is crucial for preventing reinfection or reducing disease severity. T-cells’ long-term protection, elicited either by COVID-19 vaccines or natural infection, has been extensively studied thus far; however, it is still attracting considerable scientific interest. The aim of the present epidemiological study was to define the levels of T-cellular immunity response in a specific group of unvaccinated individuals from the general population with a prior confirmed COVID-19 infection and no measurable levels of IgG antibodies. Methods: We performed a retrospective descriptive analysis of data collected from the medical records of consecutive unvaccinated individuals recovered from COVID-19, who had proceeded to a large private medical center in the Attica region from September 2021 to September 2022 in order to be examined on their own initiative for SARS-CoV-2 T-cell immunity response. The analysis of T-cell responses was divided into three time periods post infection: Group A: up to 6 months; Group B: 6–12 months; Group C: >12 months. The SARS-CoV-2 T-cell response was estimated against spike (S) and nucleocapsid (N) structural proteins by performing the T-SPOT. COVID test methodology. SARS-CoV-2 IgG antibody levels were measured by the SARS-CoV-2 IgG II Quant assay (Abbott Diagnostics). Results: A total of 182 subjects were retrospectively included in the study, 85 females (46.7%) and 97 (53.3%) males, ranging from 19 to 91 years old (mean 50.84 ± 17.2 years). Among them, 59 (32.4%) had been infected within the previous 6 months from the examination date (Group A), 69 (37.9%) had been infected within a time period > 6 months and <1 year (Group B) and 54 (29.7%) had been infected within a time period longer than 1 year from the examination date (Group C). Among the three groups, a positive T-cell reaction against the S antigen was reported in 47/58 (81%) of Group A, 61/69 (88.4%) of Group B and 40/54 (74.1%) of Group C (chi square, p = 0.27). T-cell reaction against the N antigen was present in 45/58 (77.6%) of Group A, 61/69 (88.4%) of Group B and 36/54 (66.7%) of Group C (chi square, p = 0.02). The median Spot-Forming Cells (SFC) count for the S antigen was 18 (range from 0–160) in Group A, 19 (range from 0–130) in Group B and 17 (range from 0–160) in Group C (Kruskal–Wallis test, p = 0.11; pairwise comparisons: groups A–B, p = 0.95; groups A–C, p = 0.89; groups B–C, p = 0.11). The median SFCs count for the N antigen was 14.5 (ranging from 0 to 116) for Group A, 24 (ranging from 0–168) in Group B and 16 (ranging from 0–112) for Group C (Kruskal–Wallis test, p = 0.01; pairwise comparisons: groups A–B, p = 0.02; groups A–C, p = 0.97; groups B–C, p = 0.03). Conclusions: Our data suggest that protective adaptive T-cellular immunity following natural infection by SARS-CoV-2 may persist for over 12 months, despite the undetectable humoral element. Full article

Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity. Full article

Neuraminidase (NA)-based immunity could reduce the harmful impact of novel antigenic variants of influenza viruses. The detection of neuraminidase-inhibiting (NI) antibodies in parallel with anti-hemagglutinin (HA) antibodies may enhance research on the immunogenicity and duration of antibody responses to influenza vaccines. To assess anti-NA antibodies after vaccination with seasonal inactivated influenza vaccines, we used the enzyme-linked lectin assay, and anti-HA antibodies were detected in the hemagglutination inhibition assay. The dynamics of the anti-NA antibody response differed depending on the virus subtype: antibodies to A/H3N2 virus neuraminidase increased later than antibodies to A/H1N1pdm09 subtype neuraminidase and persisted longer. In contrast to HA antibodies, the fold increase in antibody titers to NA after vaccination poorly depended on the preexisting level. At the same time, NA antibody levels after vaccination directly correlated with titers before vaccination. A difference was found in response to NA antigen between split and subunit-adjuvanted vaccines and in NA functional activity in the vaccine formulations. Full article

The declaration of the conclusion of the COVID-19 pandemic notwithstanding, coronavirus remains prevalent in circulation, and the potential emergence of novel variants of concern introduces the possibility of new outbreaks. Moreover, it is not clear how quickly and to what extent the effectiveness of vaccination will decline as the virus continues to mutate. One possible solution to combat the rapidly mutating coronavirus is the creation of safe vaccine platforms that can be rapidly adapted to deliver new, specific antigens in response to viral mutations. Recombinant probiotic microorganisms that can produce viral antigens by inserting specific viral DNA fragments into their genome show promise as a platform and vector for mucosal vaccine antigen delivery. The authors of this study have developed a convenient and universal technique for inserting the DNA sequences of pathogenic bacteria and viruses into the gene that encodes the pili protein of the probiotic strain E. faecium L3. The paper presents data on the immunogenic properties of two E. faecium L3 vaccine strains, which produce two different fragments of the coronavirus S1 protein, and provides an assessment of the protective efficacy of these oral vaccines against coronavirus infection in Syrian hamsters. Full article

(1) Background: SARS-CoV-2 T cell immunity is rapidly activated following SARS-CoV-2 infection and vaccination and is crucial for controlling infection progression and severity. The aim of the present study was to compare the levels of T cell responses to SARS-CoV-2 between cohorts of subjects with hybrid immunity (convalescent and vaccinated), vaccinated naïve (non-exposed) and convalescent unvaccinated subjects. (2) Methods: We performed a retrospective descriptive analysis of data collected from the medical records of adult individuals who were consecutively examined at a large, private Medical Center of Attica from September 2021 to September 2022 in order to be examined on their own initiative for SARS-CoV-2 T cell immunity response. They were divided into three groups: Group A: SARS-CoV-2 convalescent and vaccinated subjects; Group B: SARS-CoV-2 naïve vaccinated subjects; Group C: SARS-CoV-2 convalescent unvaccinated subjects. The SARS-CoV-2 T cell response was estimated against spike (S) and nucleocapsid (N) structural proteins by performing the methodology T-SPOT.COVID test. (3) Results: A total of 530 subjects were retrospectively included in the study, 252 females (47.5%) and 278 (52.5%) males ranging from 13 to 92 years old (mean 55.68 ± 17.0 years). Among them, 66 (12.5%) were included in Group A, 284 (53.6%) in Group B and 180 (34.0%) in Group C. Among the three groups, a reaction against S antigen was reported in 58/66 (87.8%) of Group A, 175/284 (61.6%) of Group B and 146/180 (81.1%) of Group C (chi-square, p < 0.001). Reaction against N antigen was present in 49/66 (74.2%) of Group A and in 140/180 (77.7%) of Group C (chi-square, p = 0.841). The median SFC count for S antigen was 24 (range from 0–218) in Group A, 12 (range from 0–275) in Group B and 18 (range from 0–160) in Group C (Kruskal–Wallis test, p < 0.001; pairwise comparisons: groups A–B, p < 0.001; groups A–C, p = 0.147; groups B–C, p < 0.001). The median SFCs count for N antigen was 13 (range 0–82) for Group A and 18 (range 0–168) for Group C (Kruskal–Wallis test, p = 0.27 for A–C groups). (4) Conclusions: Our findings suggest that natural cellular immunity, either alone or combined with vaccination, confers stronger and more durable protection compared to vaccine-induced cellular immunity. Full article

This study aimed at producing an updated assessment of the incidence of anaphylaxis associated with COVID-19 vaccines based on pharmacovigilance data. Anaphylactic reaction and anaphylactic shock data post-COVID-19-vaccination reported from week 52, 2020 to week 1 or week 2, 2023 were collected from the VAERS and EudraVigilance databases, respectively, and analyzed comparatively. Incidence rates were calculated using the corresponding administered vaccine doses as denominators for all licensed vaccines and both platform types (mRNA or vectored). The latest data from the present analysis showed lower anaphylaxis incidence associated with COVID-19 vaccination compared to previous estimates from week 52, 2020 to week 39, 2021 (anaphylactic reaction: 8.96 (95% CI 8.80–9.11)/million doses overall (EEA: 14.19 (95% CI 13.92–14.47)/million/US: 3.17 (95% CI 3.03–3.31)/million); anaphylactic shock: 1.46 (95% CI 1.39–1.52)/million doses overall (EEA: 2.47 (95% CI 2.36–2.58)/million/US: 0.33 (95% CI 0.29–0.38)/million)). Incidence rates varied by vaccine and were higher as captured in EudraVigilance compared to the VAERS and for vectored compared to mRNA vaccines. Most reported cases had a favorable outcome. The extremely rare fatalities (overall rates across continents 0.04 (95% CI 0.03–0.06)/million doses for anaphylactic reaction and 0.02 (95% CI 0.01–0.03)/million vaccine doses for anaphylactic shock) were also associated with vector-rather than mRNA-based vaccines. The diminished incidence of anaphylaxis post-vaccination with COVID-19 vaccines offers assurance about their safety, as does the continuous potential adverse events monitoring through specialized pharmacovigilance databases. Full article

Children are at risk of infection from severe acute respiratory syndrome coronavirus-2 virus (SARS-CoV-2) resulting in coronavirus disease (COVID-19) and its more severe forms. New-born infants are expected to receive short-term protection from passively transferred maternal antibodies from their mothers who are immunized with first-generation COVID-19 vaccines. Passively transferred antibodies are expected to wane within first 6 months of infant’s life, leaving them vulnerable to COVID-19. Live attenuated vaccines, unlike inactivated or viral-protein-based vaccines, offer broader immune engagement. Given effectiveness of live attenuated vaccines in controlling infectious diseases such as mumps, measles and rubella, we undertook development of a live attenuated COVID-19 vaccine with an aim to vaccinate children beyond 6 months of age. An attenuated vaccine candidate (dCoV), engineered to express sub-optimal codons and deleted polybasic furin cleavage sites in the spike protein of the SARS-CoV-2 WA/1 strain, was developed and tested in hamsters. Hamsters immunized with dCoV via intranasal or intramuscular routes induced high levels of neutralizing antibodies and exhibited complete protection against the SARS-CoV-2 wild-type isolates, i.e., the Wuhan-like (USA-WA1/2020) and Delta variants (B.1.617.2) in a challenge study. In addition, the dCoV formulated with the marketed measles–rubella (MR) vaccine, designated as MR-dCoV, administered to hamsters via intramuscular route, also protected against both SARS-CoV-2 challenges, and dCoV did not interfere with the MR vaccine-mediated immune response. The safety and efficacy of the dCoV and the MR-dCoV against both variants of SARS-CoV-2 opens the possibility of early immunization in children without an additional injection. Full article

Post-renal-transplant patients have a relatively low antibody-acquisition rate following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. In this study, antibody titers were measured 5–6 months and 3 weeks to 3 months after the second and third SARS-CoV-2 mRNA vaccinations, respectively. Post-renal-transplant patients visiting our hospital who had received three SARS-CoV-2 mRNA vaccine doses were included in the study. SARS-CoV-2 immunoglobulin G antibody titers were measured three times: between 3 weeks and 3 months after the second vaccination, 5–6 months after the second vaccination, and between 3 weeks and 3 months after the third vaccination. A total of 62 (40 men and 22 women) were included, 44 of whom (71.0%) were antibody positive after their third vaccination. On comparing the antibody-acquired and antibody-non-acquired groups, body mass index (BMI, odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.07–1.93, p < 0.05) and the estimated glomerular filtration rate (eGFR, OR: 1.14, 95% CI: 1.06–1.24, p < 0.01) were associated with antibody acquisition. Therefore, in Japanese post-kidney-transplant patients, increases in the antibody-acquisition rate and absolute antibody titer after the third vaccination were observed, with BMI and eGFR associated with the antibody-acquisition rate. Full article

Vaccinations have helped to control the COVID-19 pandemic; however, few studies focus on the adverse effects and allergic reactions of these vaccines and fewer have a scope in the Latin American population. The objective of this study was to assess the associations between vaccinations, sex, age, allergic reactions, and adverse effects. This was an analytical cross-sectional study conducted between 1 July and 1 October 2022. The sample consisted of 443 surveyed participants, with a total of 1272 COVID-19 vaccine doses. Seven vaccines (Pfizer BioNTech, Oxford-AstraZeneca, CanSino, Moderna, Johnson and Johnson, Sinovac, and Sputnik V) were evaluated. A total of 12.6% of those surveyed had at least one allergic reaction posterior to vaccination, and females had a greater chance of developing one (p < 0.001, OR 3.1). The most common allergic reaction was chest pain, and Pfizer-BioNTech and Oxford-AstraZeneca were associated with the onset of allergic reactions (p < 0.005). A total of 54.6% of those surveyed developed adverse effects, the most common of which were myalgia, fever, cephalea, asthenia or adynamia, and arthralgia; moreover, older age was associated with the onset of adverse effects (p < 0.5). This study concludes that the BNT162b2 (Pfizer BioNTech) and ChAdOX1 nCOV-19 (Oxford-AstraZeneca) vaccines are strongly associated with the onset of allergic reactions, with ORs of 1.6 (CI 95%, 1.18 to 2.3) and 1.87 (CI 95%, 1.35 to 2.6), respectively. In addition, females have a greater chance of developing allergic reactions associated with COVID-19 vaccinations, and there was a relation found between older age and a greater prevalence of comorbidities, adverse effects after vaccination, and COVID-19 infection after vaccination. Full article