Laboratory and Field Assessments of Oral Vibrio Vaccine Indicate the Potential for Protection against Vibriosis in Cultured Marine Fishes

Vibriosis is one of the most common threats to farmed grouper; thus, substantial efforts are underway to control the disease. This study presents an oral vaccination against multiple Vibrio spp. in a marine fish with double booster immunisation. The Vibrio harveyi strain VH1 vaccine candidate was selected from infected groupers Epinephelus sp. in a local farm and was formalin inactivated and combined with commercial feed at a 10% ratio (v/w). A laboratory vaccination trial was conducted for seventy days. The induction of IgM antibody responses in the serum of Asian seabass Lates calcarifer immunised with the oral Vibrio harveyi strain VH1 was significantly (p < 0.05) increased as early as week one post-primary vaccination. Subsequent administration of the first and second booster for 5 consecutive days, starting on days 14 and 42, respectively, improved the specific antibody level and reached a highly significant (p < 0.05) value at days 35 and 49 before slightly decreasing from day 56 onwards. Antibody titres of the control unvaccinated group remained relatively stable and low throughout the experimental period. At the end of the 70-day vaccination trial, 23 days post final boost, an intraperitoneal challenge with a field strain of Vibrio harveyi, V. alginolyticus, and V. parahaemolyticus was carried out. Our challenge study showed that oral Vibrio harveyi strain VH1 vaccine candidate could induce significant protection, with an RPS of 70–80% against different Vibrio species. Thereafter, a field trial was conducted in a mariculture farm to study the effect of field vaccination using the oral Vibrio harveyi strain VH1 vaccine candidate. A total of 3000 hybrid grouper juveniles were divided into two groups in triplicate. Fish of Group 1 were not vaccinated, while Group 2 were vaccinated with the feed-based vaccine. Vaccinations were carried out on days 0, 14, and 42 via feeding the fish with the vaccine at 4% body weight for 5 consecutive days. At the end of the study period, the fish survival rate was 80% for the vaccinated group, significantly (p < 0.05) higher than the 65% seen in the control unvaccinated group. Furthermore, the vaccinated fish showed significantly (p < 0.05) better growth performances. Therefore, the oral Vibrio vaccine from the inactivated Vibrio harveyi strain VH1 is a potential versatile vaccine candidate that could stimulate good immune responses and confer high protection in both Asian seabass, Lates calcarifer, and farm hybrid grouper Epinephelus fuscoguttatus × Epinephelus lanceolatus.

Durability of Protection against COVID-19 Breakthrough Infections and Severe Disease by Vaccines in the United States

Objectives: Determine durability of protection by the three currently available COVID-19 vaccines in the United States (US) following primary vaccination against breakthrough infections, hospitalizations, and intensive care unit (ICU) admissions. Methods: Using claims and laboratory data covering 168 million lives, we conducted a matched case-control study with fully vaccinated individuals between January 1 and September 7, 2021. Odds ratios (OR) for developing outcomes in months two through six following full vaccination were estimated relative to the first month after full vaccination for each vaccine separately. Results: Evidence of waning protection against infections started in month 2 from vaccination for both BNT162b2 (OR [95% CI] in month 6+, 2.93 [2.72, 3.15]) and mRNA-1273 (OR [95% CI] in month 6+, 2.76 [2.51, 3.04]), and in month 4 for Ad26.COV2.S (OR [95% CI] in month 5+, 1.31 [1.18, 1.47]). Evidence of waning protection against hospitalization started in month 2 for BNT162b2 (OR [95% CI], 3.97 [3.26, 4.83] in month 6+) and in month 3 for mRNA-1273 (OR 95% CI, 1.66 [1.26, 2.19] in month 6+). There was no evidence of waning protection against hospitalization for Ad26.COV2.S (OR [95% CI], 1.25 [0.86, 1.80] in month 5+). No waning of protection was observed at any time for ICU admissions for all three vaccines. Conclusions: Following primary vaccination, all three vaccines showed strong and durable protection against ICU admissions. Ad26.COV2.S showed a more durable level of protection against breakthrough infections and hospitalizations in line with published evidence of its durable antibody and cellular immune response, although its Vaccine Effectiveness (VE) at baseline after a single-dose is lower than that for the two-dose mRNA vaccines. Additional studies are needed to understand durability following homologous or heterologous boosters.

COVID-19 vaccination is highly effective to prevent SARS-CoV-2 circulation

Background: We provide here an analysis of effectiveness of primary coronavirus disease 2019 (COVID-19) vaccination and COVID-19 vaccine booster doses in preventing severe acute respiratory syndrome coronavirus 2 (COVID-19) infection.Methods: We retrieved information on COVID-19 vaccination and newly diagnosed cases of SARS-CoV-2 infection from the weekly official report of the Italian National Institute of Health (Istituto Superiore di Sanità, ISS; Last available update, January 1, 2022).Results: At the time of our analysis, 39.9 million people completed a primary COVID-19 vaccination cycle, of whom 13.6 million (34.0%) <5 months from the last dose, whilst 5.7 million had also received COVID-19 vaccine booster doses. The risk of SARS-CoV-2 infection was 71% (OR, 0.29; 95%CI, 0.29-0.29) and 86% (OR, 0.14; 95%CI, 0.14-0.14) lower in people who received primary vaccination <5 months and booster doses <5 months compared to the unvaccinated population, but was also half (OR, 0.49; 95%CI, 0.48-0.49) in those who received booster doses <5 months compared to those who completed the primary vaccination <5 months.Conclusions: These results attest that COVID-19 vaccines not only reduce the risk of developing severe illness in patients with SARS-CoV-2 infection, but shall also be considered reliable and effective means to limit virus circulation within the general population.

Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients

Importance: Data on the humoral and cellular immune response to primary and booster SARS-CoV-2 vaccination in immunosuppressed patients is limited. Objective: To determine humoral and cellular response to primary and booster vaccination in immunosuppressed patients and identify variables associated with poor response. Design: Retrospective observational cohort study. Setting: Large healthcare system in Northern California. Participants: This study included patients fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) who underwent clinical testing for anti-SARS-SoV-2 S1 IgG ELISA (anti-S1 IgG) and SARS-CoV-2 interferon gamma release assay (IGRA) from January 1, 2021 through November 15, 2021. A cohort of 18 immunocompetent volunteer healthcare workers were included as reference. No participants had a prior diagnosis of SARS-CoV-2 infection. Exposure(s): Immunosuppressive diseases and therapies. Main Outcome(s) and Measure(s): Humoral and cellular SARS-CoV-2 vaccine response as measured by anti-S1 IgG and SARS-CoV-2 IGRA, respectively, after primary and booster vaccination. Results: 496 patients (54% female; median age 50 years) were included in this study. Among immunosuppressed patients after primary vaccination, 62% (261/419) had positive anti-S1 IgG and 71% (277/389) had positive IGRA. After booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Immunosuppressive factors associated with low rates of humoral response after primary vaccination included anti-CD20 monoclonal antibodies (n=48, P<.001), sphingosine 1-phsophate (S1P) receptor modulators (n=11, P<.001), mycophenolate (n=78, P=.002), and B cell lymphoma (n=55, P=.004); those associated with low rates of cellular response included S1P receptor modulators (n=11, P<.001) and mycophenolate (n=69, P<.001). Of patients who responded poorly to primary vaccination, 16% (4/25) with hematologic malignancy or primary immunodeficiency developed a significantly increased humoral response after the booster dose, while 52% (14/27) with solid malignancy, solid organ transplantation, or autoimmune disease developed an increased response (P=.009). Only 5% (2/42) of immunosuppressed patients developed a significantly increased cellular response following the booster dose. Conclusions and Relevance: Cellular vaccine response rates were higher than humoral response rates in immunosuppressed individuals after primary vaccination, particularly among those undergoing B cell targeting therapies. However, humoral response can be increased with booster vaccination, even in patients on B cell targeting therapies.

Immunization of Nile tilapia (Oreochromis niloticus) Broodstock With Tilapia Lake Virus (TiLV) Inactivated Vaccines Elicits Protective Antibody and Passive Maternal Antibody Transfer

Tilapia lake virus (TiLV), a major pathogen of farmed tilapia, is known to be vertically transmitted. Here, we hypothesize that Nile tilapia (Oreochromis niloticus) broodstock immunized with a TiLV inactivated vaccine can mount a protective antibody response and passively transfer maternal antibodies to their fertilized eggs and larvae. To test this hypothesis, three groups of tilapia broodstock, each containing 4 males and 8 females, were immunized with either a heat-killed TiLV vaccine (HKV), a formalin-killed TiLV vaccine (FKV) (both administered at 3.6 &times;106 TCID50 per fish), or with L15 medium. Booster vaccination with the same vaccines was given 3-weeks later, and mating took place 1 week thereafter. Broodstock blood sera, fertilized eggs and larvae were collected from 6-14 weeks post-primary vaccination for measurement of TiLV-specific antibody (anti-TiLV IgM) levels. In parallel, passive immunization using sera from the immunized female broodstock was administered to na&iuml;ve tilapia juveniles to assess if antibodies induced in immunized broodstock were protective. The results showed that anti-TiLV IgM was produced in the majority of both male and female broodstock vaccinated with either the HKV or FKV and that and that these antibodies could be detected in the fertilized eggs and larvae from vaccinated broodstock. Higher levels of maternal antibody were observed in fertilized eggs from broodstock vaccinated with HKV than those vaccinated with FKV. Low levels of TiLV-IgM were detected in some of the 1-3-day old larvae but were undetectable in 7-14-day old larvae from the vaccinated broodstock, indicating a short persistence of TiLV-IgM in larvae. Moreover, passive immunization proved that antibodies elicited by TiLV vaccination were able to confer 85% to 90% protection against TiLV challenge in na&iuml;ve juvenile tilapia. In conclusion, immunization of tilapia broodstock with TiLV vaccines could be a potential strategy for the prevention of TiLV in tilapia fertilized eggs and larvae, with HKV appearing to be more promising than FKV for maternal vaccination.

Attitudes of Poles towards the COVID-19 Vaccine Booster Dose: An Online Survey in Poland

Introduction: COVID-19 vaccination has now become the most effective way to combat the pandemic, but there is a gradual decline in the protection that it offers over time. Therefore, the Food and Drug Administration (FDA) and EMA now recommend the use of the so-called booster dose, especially in at-risk groups. The purpose of the study was to assess the attitudes of Poles towards the recommendation to receive a booster dose of the COVID-19 vaccine and to evaluate the main reasons for refusing or delaying the decision. Material and methods: The study was based on a proprietary questionnaire distributed via the Internet. There were 1598 respondents, 54 of which did not consent to participate in the survey and/or did not complete the vaccination against SARS-CoV-2. As a result, 1528 surveys were included in the final analysis. The vast majority of the respondents, namely 1275 (83.4%), were female, and 772 (50.5%) were residents of cities with a population of over 250,000. Results: Out of all respondents, 38 (2.5%) had already received the COVID-19 vaccine booster dose and 1031 (67.4%) would like to receive it as soon as possible. Forty-five (2.9%) respondents reported that they were completely unwilling to take the booster dose. The occurrence of adverse events after primary vaccination were reported by 79.9% of the survey participants. The most common reasons why the respondents refused to be vaccinated are lack of confidence in the effectiveness of the booster dose and the occurrence of adverse events in them or their loved ones. Age, gender, residence, or relationship status were not shown to affect attitudes towards the expansion of the basic vaccination schedule. Conclusions: One in three respondents plans to delay or refrain from taking the COVID-19 vaccine booster dose. The main reason for refusal to be vaccinated is the belief that the previous vaccination provides sufficient protection.

Boosting Humoral Immunity from mRNA COVID-19 Vaccines in Kidney Transplant Recipients

Introduction: The immune response to the primary (two-dose) series of mRNA COVID-19 vaccines in kidney transplant recipients (KTRs) is very weak. We conducted a longitudinal observational study to compare the humoral response to a third, additional primary dose of mRNA vaccines between infection-naïve (IN-KTRs) and previously infected KTRs (PI-KTRs). Methods: We measured the levels of anti-spike (anti-s) IgG antibodies before and 14–21 days after the third dose and, in the secondary analysis, we compared the antibody response to BNT162b2 versus mRNA-1273. The reactogenicity assessment included solicited local and systemic reactions. Results: A total of 112 KTRs were enrolled, including 83 IN-KTR and 29 PI-KTR, among whom seroconversion in anti-s antibodies after the primary two-dose vaccination was achieved in 45.78% and 100% of cases, respectively. After three months, a waning antibodies titer by 67.4% (IN-KTR) and 7.5% (PI-KTR) was observed. After the third dose of the mRNA vaccine, 71.08% (59/83) of IN-KTR and 96.5% (28/29) of PI-KTR samples were seroconverted with a median anti-s titer of 468.0 (195.0–1620.0) BAU/mL and 1629.0 (1205–1815) BAU/mL, respectively. Of those IN-KTR in whom the primary vaccination failed, 46.67% (21/45) of patients achieved seroconversion after the third dose. No serious adverse events after the third dose were reported. In strata analyses, after the third dose, 66% (40/60) of patients vaccinated with BNT162b2 and 82.6% (19/23) of patients vaccinated with mRNA-1273 seroconverted with a median anti-s titer of 384.5 (144–837) BAU/mL and 1620 (671–2040) BAU/mL, respectively. Conclusions: The use of a third dose of mRNA vaccine may be of benefit for KTR, especially for those in whom the primary vaccination failed. Vaccines with a higher dose of mRNA and a longer interval between doses of the primary vaccination, such as mRNA-1273, seem to be the preparations of choice in immunocompromised individuals.

Immunogenicity and Safety Following a Homologous Booster Dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): A Phase 2 Randomized Placebo-Controlled Trial

Background Emerging SARS-CoV-2 variants and evidence of waning vaccine efficacy present significant obstacles toward controlling the COVID-19 pandemic. Booster doses of SARS-CoV-2 vaccines may address these concerns by both amplifying and broadening the immune responses seen with initial vaccination regimens. Methods In a phase 2 study, a single booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M adjuvant (NVX-CoV2373) was administered to healthy adult participants 18 to 84 years of age approximately 6 months following their primary two-dose vaccination series. Safety and immunogenicity parameters were assessed, including assays for IgG, MN50, and hACE2 receptor binding inhibition against the ancestral SARS-CoV-2 strain and select variants (B.1.351 [Beta], B.1.1.7 [Alpha], B.1.617.2 [Delta], and B.1.1.529 [Omicron]). This trial is registered with ClinicalTrials.gov, NCT04368988. Findings An incremental increase in the incidence of solicited local and systemic reactogenicity events was observed with subsequent vaccinations. Following the booster, incidence rates of local and systemic reactions were 82.5% (13.4% ≥ Grade 3) and 76.5% (15.3% ≥ Grade 3), respectively, compared to 70.0% (5.2% ≥ Grade 3) and 52.8% (5.6% ≥ Grade 3), respectively, following the primary vaccination series. Events were primarily mild or moderate in severity and transient in nature, with a median duration of 1.0 to 2.5 days. Immune responses seen 14 days following the primary vaccination series were compared with those observed 28 days following the booster (Day 35 and Day 217, respectively). For the ancestral SARS-CoV-2 strain, serum IgG geometric mean titers (GMTs) increased ~4.7-fold from 43,905 ELISA units (EU) at day 35 to 204,367 EU at Day 217. Neutralization (MN50) assay GMTs showed a similar increase of ~4.1-fold from 1,470 at day 35 to 6,023 at Day 217. A functional hACE2 receptor binding inhibition assay analyzing activity against ancestral and variant strains of SARS-CoV-2 at Day 189 vs Day 217 found 54.4-fold (Ancestral), 21.9 fold (Alpha), 24.5-fold (Beta), 24.4-fold (Delta), and 20.1-fold (Omicron) increases in titers. An anti-rS IgG activity assay comparing the same time points across the same SARS-CoV-2 strains found titers improved 61.2-fold, 85.9-fold, 65.0-fold, 92.5 fold, and 73.5 fold, respectively. Interpretation Administration of a booster dose of NVX-CoV2373 approximately 6 months following the primary vaccination series resulted in an incremental increase in reactogenicity along with enhanced immune responses. For both the prototype strain and all variants evaluated, immune responses following the booster were notably higher than those associated with high levels of efficacy in phase 3 studies of the vaccine.

Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre study analysis by age-group, vaccine brand and time since vaccination, I-MOVE-COVID-19 and ECDC networks, July–August 2021

IntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. We measured COVID-19 vaccine effectiveness (VE) against symptomatic infection, using a multicentre test-negative study at primary care/community level in Europe.MethodsPatients presenting with COVID-19/ARI symptoms at primary care/community level in 10 countries were tested for SARS-CoV-2. We measured complete primary course overall VE among those aged 30–44, 45–59, 60–74 and ≥75 years, and among those 30–59 and ≥60 years by vaccine brand and by time since vaccination.ResultsOverall VE was 74% (95%CI: 69–79), 76% (95%CI: 71–80), 63% (95%CI: 48–75), 63% (95%CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥75 years, respectively. VE among those aged 30–59 years was 78% (95%CI: 75–81), 66% (95%CI: 58–73), 91% (95%CI: 87–94) and 52% (95%CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among those aged ≥60 years was 67% (95%CI: 52–77), 65% (95%CI: 48–76), 83% (95%CI: 64–92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30–59 years was 87% (95%CI: 83–89) and 65% (95%CI: 56–71%) at 14–29 days and ≥90 days between vaccination and onset of symptoms, respectively.ConclusionsVE against the symptomatic SARS-CoV-2 Delta variant infection varied among brands, ranging from 52–91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% ≥90 days between vaccination and onset.

Seroconversion rate after primary vaccination with two doses of BNT162b2 versus mRNA-1273 in solid organ transplant recipients: a systematic review and meta-analysis

In the general population, the seroconversion rate after primary vaccination with two doses of anti-SARS-CoV-2 mRNA vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here, we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients. A systematic literature research was performed in Pubmed, Web of Science, and the Cochrane library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated. Six studies that described the development of antibodies against receptor-binding domain (RBD) and/or S1 subunit of the spike protein were eligible for meta-analysis. Two of them also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 (45.2%; 95% confidence interval (CI) 32.5%-58.3%) than patients vaccinated with two doses of mRNA-1273 (60.4%; 95% CI 47.4%-72.7%. The relative seroconversion rate amounted 0.79 (95% CI 0.71-0.88). This systematic review and meta-analysis indicates that, in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared to BNT162b2.