A Combination of Deworming and Prime-Boost Vaccination Regimen Restores Efficacy of Vaccination Against Influenza in Helminth-Infected Mice

Helminths still infect a quarter of the human population. They manage to establish chronic infections by downmodulating the immune system of their hosts. Consequently, the immune response of helminth-infected individuals to vaccinations may be impaired as well. Here we study the impact of helminth-induced immunomodulation on vaccination efficacy in the mouse system. We have previously shown that an underlying Litomosoides sigmodontis infection reduced the antibody (Ab) response to anti-influenza vaccination in the context of a systemic expansion of type 1 regulatory T cells (Tr1). Most important, vaccine-induced protection from a challenge infection with the 2009 pandemic H1N1 influenza A virus (2009 pH1N1) was impaired in vaccinated, L. sigmodontis-infected mice. Here, we aim at the restoration of vaccination efficacy by drug-induced deworming. Treatment of mice with Flubendazole (FBZ) resulted in elimination of viable L. sigmodontis parasites in the thoracic cavity after two weeks. Simultaneous FBZ-treatment and vaccination did not restore Ab responses or protection in L. sigmodontis-infected mice. Likewise, FBZ-treatment two weeks prior to vaccination did not significantly elevate the influenza-specific Ig response and did not protect mice from a challenge infection with 2009 pH1N1. Analysis of the regulatory T cell compartment revealed that L. sigmodontis-infected and FBZ-treated mice still displayed expanded Tr1 cell populations that may contribute to the sustained suppression of vaccination responses in successfully dewormed mice. To outcompete this sustained immunomodulation in formerly helminth-infected mice, we finally combined the drug-induced deworming with an improved vaccination regimen. Two injections with the non-adjuvanted anti-influenza vaccine Begripal conferred 60% protection while MF59-adjuvanted Fluad conferred 100% protection from a 2009 pH1N1 infection in FBZ-treated, formerly L. sigmodontis-infected mice. Of note, applying this improved prime-boost regimen did not restore protection in untreated L. sigmodontis-infected mice. In summary our findings highlight the risk of failed vaccinations due to helminth infection.

Impact of Vaccination on the Sense of Security, the Anxiety of COVID-19 and Quality of Life among Polish. A Nationwide Online Survey in Poland

The pandemic state has a destructive effect on the human psyche and induces fear for one’s own health. By reducing the risk of severe COVID-19, vaccination may indirectly improve the mental state. This study aims to assess the effects of vaccination on respondents’ mental well-being, their attitudes towards adherence to government recommendations limiting viral transmission, and to identify factors that may influence the decision to get vaccinated. The survey took the form of the authors’ own, fully voluntary, anonymous, online questionnaire. Standardised psychometric tools were used in the survey: Generalised Anxiety Disorder Assessment (GAD-7) and Manchester Short Assessment of Quality of Life (MANSA). The survey involved 1696 respondents, the vast majority of whom were women, and were aged 18–29. The vaccination status was declared by 1677 respondents (98.9%), 430 (25.4%) of whom were vaccinated with at least one dose of vaccine, while 303 (17.9%) respondents were not only unvaccinated at all, and declared no intention to get vaccinated in the future. Fully vaccinated individuals were found to have lower levels of anxiety, higher MANSA scores and lower subjective anxiety about being infected with COVID-19 than those awaiting vaccination or those with an incomplete vaccination regimen (one dose). Those who are not willing to get vaccinated have the lowest sense of anxiety and fear of being infected and they have the lowest adherence to government recommendations limiting SARS-CoV-2 transmission. Conclusions: COVID-19 vaccination reduces the level of anxiety about being infected and anxiety due to COVID-19 disease in people from the immediate environment. Those who are not willing to get vaccinated have extreme attitudes that negate the pandemic as a whole, including the need for COVID-19 vaccination. Fully vaccinated individuals still adhere to the SARS-CoV-2 prevention policies in place.

Efficacy of a Third BNT162b2 mRNA COVID-19 Vaccine Dose in Patients with CLL who Failed Standard Two-dose Vaccination

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to COVID-19 vaccination. Here, we evaluated the antibody response to a third BNT162b2 mRNA vaccine in patients with CLL/small lymphocytic lymphoma (SLL) who failed to achieve a humoral response after standard two-dose vaccination regimen. Anti-SARS-CoV-2S and neutralizing antibodies were measured 3 weeks after administration of the third dose. In 172 patients with CLL the antibody response rate was 23.8%. Response rate among actively treated patients (12.0%, n=12/100) was lower compared to treatment-naïve patients (40.0%, n=16/40; OR=4.9, 95% CI 1.9-12.9; p<0.001) and patients off-therapy (40.6%, n=13/32; OR=5.0, 95% CI 1.8-14.1; p<0.001), (p<0.001). In those actively treated with BTK inhibitors or venetoclax ± anti-CD20 antibody, response rates were extremely low (15.3%, n=9/59 and 7.7%, n=3/39, respectively). Only one of the 28 patients (3.6%) treated with anti-CD20 antibodies <12 months prior to vaccination responded. The anti-SARS-CoV-2S antibody levels correlated linearly with neutralizing antibody titers (r=0.732, p<0.001). In a multivariate analysis, the independent variables that were associated with response included lack of active therapy (OR=5.6, 95% CI 2.3-13.8; p<0.001) and serum IgA levels ≥80 mg/dL (OR=5.8, 95% CI 2.1-15.9; p<0.001) In conclusion, in patients with CLL/SLL who failed to achieve a humoral response after standard two-dose BNT162b2 mRNA vaccination regimen, close to a quarter responded to the third dose of vaccine. The antibody response rates were lower during active treatment and in patients with a recent exposure (<12 months prior to vaccination) to anti-CD20 therapy.

A self-amplifying mRNA COVID-19 vaccine drives potent and broad immune responses at low doses that protects non-human primates against SARS-CoV-2

The coronavirus disease 2019 (COVID-19) pandemic continues to spread globally, highlighting the urgent need for safe and effective vaccines that could be rapidly mobilized to immunize large populations. We report the preclinical development of a self-amplifying mRNA (SAM) vaccine encoding a prefusion stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein and demonstrate potent cellular and humoral immune responses at low doses in mice and rhesus macaques. The homologous prime-boost vaccination regimen of SAM at 3, 10 and 30 μg induced potent neutralizing antibody titers in rhesus macaques following two SAM vaccinations at all dose levels, with the 10 μg dose generating geometric mean titers (GMT) 48-fold greater than the GMT of a panel of SARS-CoV-2 convalescent human sera. Spike-specific T cell responses were observed at all dose levels. SAM vaccination provided protective efficacy against SARS-CoV-2 challenge as both a homologous prime-boost and as a single boost following ChAd prime, demonstrating reduction of viral replication in both the upper and lower airways. Protection was most effective with a SAM prime-boost vaccination regimen at 10 and 30 μg and with a ChAd/SAM heterologous prime-boost regimen. The SAM vaccine is currently being evaluated in clinical trials as both a homologous prime-boost regimen at low doses and as a boost following heterologous prime.

Effect of heterologous vaccination regimen with Ad5-nCoV CanSinoBio and BNT162b2 Pfizer in SARS-CoV-2 IgG antibodies titers

IntroductionThe efficacy with one dose Ad5-nCoV has been concerned. As a result, some patients have self-reported getting a boost with BNT. Therefore, this study aimed to compare SARS-CoV-2 spike 1-2 IgG antibodies in plasma samples between two groups: one group immunized with Ad5-nCoV and another with a heterologous vaccination regimen with Ad5-nCoV and BNT.MethodsProspective observational study included a subgroup analysis of patients who received the Ad5-nCoV immunization during the first trimester of 2021 in a Northern city of Mexico; and agreed to a follow-up for an entire year through SARS-CoV-2 specific IgG antibodies measurement samples. During the three months follow-up, some patients self-reported receiving a BNT boost. We report IgG levels from basal, 21-28 days after Ad5-nCoV dose, three months, and an additional 21-28 days after BNT boost.ResultsSeventeen patients 40 (16) years old, 52.9% men, were analyzed. We created four groups: (G1) patients vaccinated with Ad5-nCoV with no history of SARS-COV-2 (n=4), (G2) patients vaccinated with Ad5-nCoV and the first shot of BNT with no history of SARS-COV-2 (n=6), (G3) patients vaccinated with Ad5-nCoV with history of SARS-COV-2 (n=5), and (G4) patients vaccinated with Ad5-nCoV and the first shot of BNT with history of SARS-COV-2 (n=2).The group immunized with a heterologous vaccine scheme reported higher antibodies after 21-28 days of follow-up after BNT boost. Median (IQR): G1 46.7 (-), G2 1077.5 (1901), G3 1158.5 (2673.5), and G4 2090 (-) (p<0.05). Headache was the most frequent adverse reaction when patients received Ad5-nCoV (n = 10, 83%), and pain at the injection site was the most frequent adverse reaction with BNT boost (n = 5, 83.3%).ConclusionPatients receiving a BNT boost after Ad5-nCoV had higher SARS-CoV-2 spike 1-2 IgG antibodies titers with no severe adverse reaction.Author Approvalall authors read an approved the final version of the manuscriptCompeting InterestsThe authors have declared no competing interestFundingThe research was supported by private funding provided by the hospital. No external funding was used.Ethics statementEthics committee/local Institutional Review Board from the school of Medicine from Universidad de Monterrey gave ethical approval: Ref.:26022021-CN-1e-CI

Humoral Response Induced by Prime-Boost Vaccination with the ChAdOx1 nCoV-19 and mRNA BNT162b2 Vaccines in a Teriflunomide-Treated Multiple Sclerosis Patient

Patients with multiple sclerosis (MS) are treated with drugs that may impact immune responses to SARS-CoV-2 vaccination. Evaluation of “prime-boost” (heterologous) vaccination regimens including a first administration of a viral vector-based vaccine and a second one of an mRNA-based vaccine in such patients has not yet been completed. Here, we present the anti-spike protein S humoral response, including the neutralizing antibody response, in a 54-year-old MS patient who had been treated with teriflunomide for the past 2 years and who received a heterologous ChAdOx1 nCoV-19/ BNT162b2 vaccination regimen. The results showed a very strong anti-S IgG response and a good neutralizing antibody response. These results show that teriflunomide did not prevent the development of a satisfactory humoral response in this MS patient after vaccination with a ChAdOx1 nCoV-19/ BNT162b2 prime-boost protocol.

Immunogenicity and efficacy of heterologous ChadOx1/BNT162b2 vaccination

Following severe adverse reactions in patients vaccinated with the AstraZeneca ChadOx1 (Chad) vaccine, European health authorities have recommended that patients under the age of 55 who received one dose of Chad vaccine receive a second dose of Pfizer BNT162b2 (BNT) vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here, we show that the heterologous Chad/BNT combination confers better protection against SARS-CoV-2 infection than the homologous BNT/BNT combination in a population of health care workers. To understand the underlying mechanism, we monitored in a longitudinal way the anti-spike immunity conferred by each vaccinal combination. Both combinations induced strong anti-spike antibody responses after boost in all vaccinated individuals. However, sera from heterologous vaccinated individuals displayed a stronger neutralizing activity, regardless of the SARS-CoV-2 variant analyzed, and this was associated with more switched memory RBD-specific B cells with an activated phenotype and less IgA. The Chad vaccine induced a stronger T cell response than the BNT vaccine after the priming dose, and the reciprocal was true for the IgG response, which could explain the complementarity of both vaccines when used in an heterologous setting. This strongly protective vaccination regimen could be therefore particularly suitable for immunocompromised individuals.

Antibody Response Following a Two-Dose mRNA Vaccination Regimen, in Health Care Workers of a Tertiary Hospital in Athens, Greece

We analyzed the antibody responses of 564 hospital workers in Athens, Greece, after vaccination with two doses of the BNT162b2 (Comirnaty®; BioNTech and Pfizer) mRNA COVID-19 vaccine. A greater antibody increase was observed in women, younger age groups, previously infected individuals and personnel working in COVID-19 clinics. Notably, individuals with a prior COVID-19 infection mounted a significantly higher antibody titer following the first dose than the rest of the population; the same was true for those working in COVID-19 clinics, even without history of previous infection.

Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity

Background Heterologous prime-boost schedules with vector- and mRNA-based COVID-19 vaccines are already administered, but immunological responses and elicited protection have not been reported. Methods We here analyzed a cohort of 26 individuals aged 25-46 (median 30.5) years that received a ChAdOx1 nCoV-2019 prime followed by a BNT162b2 boost after an 8-week interval for reactogenicity, antibody responses and T cell reactivity. Results Self-reported solicited symptoms after ChAdOx1 nCoV-2019 prime were in line with previous reports and less severe after the BNT162b2 boost. Antibody titers increased significantly over time resulting in strong neutralization titers 2 weeks after the BNT162b2 boost. Neutralizing activity against the prevalent strain B.1.1.7 was 3.9-fold higher than in individuals receiving homologous BNT162b2 vaccination, only 2-fold reduced for variant of concern B.1.351, and similar for variant B.1.617. In addition, CD4+ and CD8+ T cells reacted to SARS-CoV-2 spike peptide stimulus 2 weeks after the full vaccination. Conclusions The heterologous ChAdOx1 nCoV-2019 / BNT162b2 prime-boost vaccination regimen is not associated with serious adverse events and results in a potent humoral immune response and elicits T cell reactivity. Variants of concern B.1.1.7, B.1.351 and B.1.617 are potently neutralized by sera of all participants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations.

Heterologous vaccination strategy for containing COVID-19 pandemic

An unequitable vaccine allocation and continuously emerging SARS-CoV-2 variants pose challenges to contain the pandemic, which underscores the need for licensing more vaccine candidates, increasing manufacturing capacity and implementing better immunization strategy. Here, we report data from a proof-of-concept investigation in two healthy individuals who received two doses of inactivated whole-virus COVID-19 vaccines, followed by a single heterologous boost vaccination after 7 months with an mRNA vaccine candidate (LPP-Spike-mRNA) developed by Stemirna Therapeutics. Following the boost, Spike-specific antibody (Ab), memory B cell and T cell responses were significantly increased. These findings indicate that a heterologous immunization strategy combining inactivated and mRNA vaccines can generate robust vaccine responses and therefore provide a rational and effective vaccination regimen.