Rituximab-to-vaccine interval on SARS-CoV-2 immunogenicity in children: The potential role of prior natural infection.

BACKGROUND: Treatment with anti-CD20 antibodies (rituximab) is used in both adults and children to treat various autoimmune and oncological diseases. Rituximab depletes B CD20+ cells and, thereby, antibody response to vaccines. This study aimed to examine the antibody response to mRNA-based COVID-19 vaccines in children aged 5-18 years undergoing rituximab treatment compared to healthy matched children. METHODS: Between 31 January and 18 July 2022, we conducted a prospective observational study at the Geneva University Hospitals, enrolling children aged 5-18 years under rituximab treatment who had received two mRNA-based SARS-CoV-2 vaccine doses. Controls were healthy volunteers with no significant medical conditions. Exclusion criteria included a recent SARS-CoV-2 infection. Blood samples were collected at day 60 (±30) and day 270 (±90) after the second vaccination. RESULTS: The rituximab-treated group exhibited significantly lower levels of antibodies specific to the anti-receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein than healthy controls at 60 (±30) days after the second vaccine dose (geometric mean concentration: 868.3 IU/mL in patients and 11,393 IU/mL in controls; p = .008). However, patients with a rituximab-to-vaccine interval shorter than 6 months and with evidence of a past infection (based on positive anti-N antibody levels) had a high level of anti-RBD antibodies. CONCLUSION: A past infection with SARS-CoV-2 may induce anti-RBD-specific memory B cells that can be re-activated by SARS-CoV-2 vaccination, even after rituximab-induced B-cell depletion. This suggests that it is possible to vaccinate earlier than 6 months after rituximab to develop a good antibody response, especially in the case of past SARS-CoV-2 infection.

Immunogenicity of Enhanced Influenza Vaccines Against Mismatched Influenza Strains in Older Adults: A Review of Randomized Controlled Trials.

Antigenic drift is a major driver of viral evolution and a primary reason why influenza vaccines must be reformulated annually. Mismatch between vaccine and circulating viral strains negatively affects vaccine effectiveness and often contributes to higher rates of influenza-related hospitalizations and deaths, particularly in years dominated by A(H3N2). Several countries recommend enhanced influenza vaccines for older adults, who are at the highest risk of severe influenza complications and mortality. The immunogenicity of enhanced vaccines against heterologous A(H3N2) strains has been examined in nine studies to date. In six studies, an enhanced, licensed MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) consistently increased heterologous antibody titers relative to standard influenza vaccine, with evidence of a broad heterologous immune response across multiple genetic clades. In one study, licensed high-dose trivalent inactivated influenza vaccine (HD-IIV3) also induced higher heterologous antibody titers than standard influenza vaccine. In a study comparing a higher dose licensed quadrivalent recombinant influenza vaccine (RIV4) with HD-IIV3 and aIIV3, no significant differences in antibody titers against a heterologous strain were observed, although seroconversion rates were higher with RIV4 versus comparators. With the unmet medical need for improved influenza vaccines, the paucity of studies especially with enhanced vaccines covering mismatched strains highlights a need for further investigation of cross-protection in older adults.

Association between Gut Microbiota Composition and Long-Term Vaccine Immunogenicity following Three Doses of CoronaVac.

BACKGROUND: Neutralizing antibody level wanes with time after COVID-19 vaccination. We aimed to study the relationship between baseline gut microbiota and immunogenicity after three doses of CoronaVac. METHODS: This was a prospective cohort study recruiting three-dose CoronaVac recipients from two centers in Hong Kong. Blood samples were collected at baseline and one year post-first dose for virus microneutralization (vMN) assays to determine neutralization titers. The primary outcome was high immune response (defined as with vMN titer ≥ 40). Shotgun DNA metagenomic sequencing of baseline fecal samples identified potential bacterial species and metabolic pathways using Linear Discriminant Analysis Effect Size (LEfSe) analysis. Univariate and multivariable logistic regression models were used to identify high response predictors. RESULTS: In total, 36 subjects were recruited (median age: 52.7 years [IQR: 47.9-56.4]; male: 14 [38.9%]), and 18 had low immune response at one year post-first dose vaccination. Eubacterium rectale (log10LDA score = 4.15, p = 0.001; relative abundance of 1.4% vs. 0, p = 0.002), Collinsella aerofaciens (log10LDA score = 3.31, p = 0.037; 0.39% vs. 0.18%, p = 0.038), and Streptococcus salivarius (log10LDA score = 2.79, p = 0.021; 0.05% vs. 0.02%, p = 0.022) were enriched in low responders. The aOR of high immune response with E. rectale, C. aerofaciens, and S. salivarius was 0.03 (95% CI: 9.56 × 10-4-0.32), 0.03 (95% CI: 4.47 × 10-4-0.59), and 10.19 (95% CI: 0.81-323.88), respectively. S. salivarius had a positive correlation with pathways enriched in high responders like incomplete reductive TCA cycle (log10LDA score = 2.23). C. aerofaciens similarly correlated with amino acid biosynthesis-related pathways. These pathways all showed anti-inflammation functions. CONCLUSION: E. rectale,C. aerofaciens, and S. salivarius correlated with poorer long-term immunogenicity following three doses of CoronaVac.

The Predictive Value of Gut Microbiota Composition for Sustained Immunogenicity following Two Doses of CoronaVac.

CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day 180 after the first dose and used chemiluminescence immunoassay to test for neutralizing antibodies (NAbs) against the receptor-binding domain (RBD) of wild-type SARS-CoV-2 virus. We performed shotgun metagenomic sequencing performed on baseline stool samples. The primary outcome was the NAb seroconversion rate (seropositivity defined as NAb ≥ 15AU/mL) at day 180. Linear discriminant analysis [LDA] effect size analysis was used to identify putative bacterial species and metabolic pathways. A univariate logistic regression model was used to derive the odds ratio (OR) of seropositivity with bacterial species. Of 119 CoronaVac recipients (median age: 53.4 years [IQR: 47.8-61.3]; male: 39 [32.8%]), only 8 (6.7%) remained seropositive at 6 months after vaccination. Bacteroides uniformis (log10LDA score = 4.39) and Bacteroides eggerthii (log10LDA score = 3.89) were significantly enriched in seropositive than seronegative participants. Seropositivity was associated with B. eggerthii (OR: 5.73; 95% CI: 1.32-29.55; p = 0.022) and B. uniformis with borderline significance (OR: 3.27; 95% CI: 0.73-14.72; p = 0.110). Additionally, B. uniformis was positively correlated with most enriched metabolic pathways in seropositive vaccinees, including the superpathway of adenosine nucleotide de novo biosynthesis I (log10LDA score = 2.88) and II (log10LDA score = 2.91), as well as pathways related to vitamin B biosynthesis, all of which are known to promote immune functions. In conclusion, certain gut bacterial species (B. eggerthii and B. uniformis) and metabolic pathways were associated with longer-term CoronaVac immunogenicity.

Intradermal Vaccination with PLGA Nanoparticles via Dissolving Microneedles and Classical Injection Needles.

PURPOSE: A dissolving microneedle array (dMNA) is a vaccine delivery device with several advantages over conventional needles. By incorporating particulate adjuvants in the form of poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) into the dMNA, the immune response against the antigen might be enhanced. This study aimed to prepare PLGA-NP-loaded dMNA and to compare T-cell responses induced by either intradermally injected aqueous-PLGA-NP formulation or PLGA-NP-loaded dMNA in mice. METHODS: PLGA NPs were prepared with microfluidics, and their physicochemical characteristics with regard to encapsulation efficiencies of ovalbumin (OVA) and CpG oligonucleotide (CpG), zeta potentials, polydispersity indexes, and sizes were analysed. PLGA NPs incorporated dMNA was produced with three different dMNA formulations by using the centrifugation method, and the integrity of PLGA NPs in dMNAs was evaluated. The immunogenicity was evaluated in mice by comparing the T-cell responses induced by dMNA and aqueous formulations containing ovalbumin and CpG (OVA/CpG) with and without PLGA NP. RESULTS: Prepared PLGA NPs had a size of around 100 nm. The dMNA formulations affected the particle integrity, and the dMNA with poly(vinyl alcohol) (PVA) showed almost no aggregation of PLGA NPs. The PLGA:PVA weight ratio of 1:9 resulted in 100% of penetration efficiency and the fastest dissolution in ex-vivo human skin (< 30 min). The aqueous formulation with soluble OVA/CpG and the aqueous-PLGA-NP formulation with OVA/CpG induced the highest CD4 + T-cell responses in blood and spleen cells. CONCLUSIONS: PLGA NPs incorporated dMNA was successfully fabricated and the aqueous formulation containing PLGA NPs induce superior CD4+ and CD8+ T-cell responses.

Should we vaccinate during an active rheumatic disease?

Timing of vaccination and its relationship with concomitant immunosuppressive therapy has been a matter of debate in the field of AutoImmune Inflammatory Rheumatic Diseases (AIIRD). Vaccination is crucial in the prevention of infections, which, in the setting of AIIRD, are known risk factors for disease flare and expose patients to increase risk of complications and mortality. As evidenced from real-life studies, vaccines do not significantly affect disease activity. Conversely, disease activity (especially in Systemic Lupus Erythematosus) may predict for vaccine response: high disease activity correlates with decreased seroconversion. For this reason, according to the EULAR 2019 recommendation, vaccination should preferably be administered during quiescent AIIRD. Beside disease activity, background immunosuppressive therapy should be considered when performing vaccination, as different Disease Modifying Anti-Rheumatic Drugs (DMARDs) decrease vaccine immunogenicity. AIIRD patients should be vaccinated, independently from the vaccine type, before starting immunosuppression. If the patient is on active immunosuppressive therapy, the best window of opportunity to boost vaccine response is during AIIRD quiescence, as low disease activity increases seroconversion and allows safe immunosuppressant spacing. In conclusion, the majority of AIIRD patients should receive vaccination, preferably during quiescent disease and taking into consideration immunosuppressant spacing.

Immunogenicity and safety of a second heterologous booster dose of NVX-CoV2373 (TAK-019) in healthy Japanese adults who had previously received a primary series of COVID-19 mRNA vaccine: Interim analysis report of a phase 3 open-label trial.

BACKGROUND: The phase 3, single-arm, open-label TAK-019-3001 study assessed two heterologous booster doses of NVX-CoV2373 administered 5 months apart in healthy Japanese adults who had completed a primary series of a COVID-19 mRNA vaccine 6-12 months previously. In the main part of this study, a first booster induced rapid and robust anti-SARS-CoV-2 immune responses, addressing waning immunity in participants. METHODS: This interim analysis evaluated the immunogenicity and safety of a second booster in the extension part of this study including comparisons with the first booster. Immunogenicity was assessed on extension day (ED) 1 (before vaccination) and ED15. Solicited and unsolicited adverse events occurring in the 7 and 28 days, respectively, after vaccination were assessed. RESULTS: Of the 150 participants who received a first NVX-CoV2373 booster, 129 were administered a second booster on ED1. Participant characteristics were consistent between the main and extension parts of the study. Titres of anti-SARS-CoV-2 rS serum immunoglobulin G and serum neutralizing antibodies against the SARS-CoV-2 ancestral strain at ED15 were 4.0- and 3.0-fold higher, respectively, than those observed 5 months after the first booster on ED1, and 3.0- and 1.4-fold higher, respectively, than those observed 14 days after the first booster on day 15. The proportions of participants who experienced solicited local and systemic adverse events (AEs) in the 7 days after the second booster were 73.6 % and 51.2 %, respectively: most were of grade 2 severity or lower. Seven percent of participants experienced unsolicited AEs in the 28 days after the second booster: all were unrelated to the treatment. There were no deaths or AEs leading to study discontinuation. DISCUSSION: A second heterologous NVX-CoV2373 booster in healthy Japanese adults induced more robust anti-SARS-CoV-2 immune responses than the first booster. The second booster was well tolerated. No new safety concerns were identified.

Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons

ABSTRACT Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

Systematic Review on the Efficacy, Effectiveness, Safety, and Immunogenicity of Monkeypox Vaccine.

BACKGROUND: The variation in the reported vaccine safety and effectiveness could contribute to the high rates of vaccine hesitancy among the general population and healthcare workers in areas where monkeypox (mpox) is circulating. In this review, our objective was to evaluate the safety, immunogenicity, effectiveness, and efficacy of the mpox vaccines. METHODS: An extensive search for articles across multiple databases was performed, including searching six databases (PubMed Central, PubMed Medline, Scopus, Web of Science, Cochrane, ProQuest), two pre-print databases (European PMC Preprint and MedRxiv), and Google Scholar. RESULTS: A total of 4290 citations were retrieved from the included databases. Following the removal of duplicates and the initial screening of records, a total of 36 studies were included into the analysis. Additionally, we identified five more studies through manual searches, resulting in a total of 41 eligible articles for qualitative synthesis. The study findings revealed that mpox vaccines demonstrate the ability to generate adequate antibodies; however, their effectiveness may decrease over time, exhibiting varying safety profiles. Most of the included studies consistently reported substantial levels of effectiveness and efficacy against mpox. Interestingly, the number of vaccine doses administered was found to influence the degree of immunogenicity, subsequently impacting the overall effectiveness and efficacy of the vaccines. Furthermore, we found that smallpox vaccines exhibited a form of cross-protection against mpox. CONCLUSIONS: Vaccines can be used to prevent mpox and effectively control its spread.

Factors Influencing Microbiota in Modulating Vaccine Immune Response: A Long Way to Go.

Vaccine immunogenicity still represents an unmet need in specific populations, such as people from developing countries and "edge populations". Both intrinsic and extrinsic factors, such as the environment, age, and dietary habits, influence cellular and humoral immune responses. The human microbiota represents a potential key to understanding how these factors impact the immune response to vaccination, with its modulation being a potential step to address vaccine immunogenicity. The aim of this narrative review is to explore the intricate interactions between the microbiota and the immune system in response to vaccines, highlighting the state of the art in gut microbiota modulation as a novel therapeutic approach to enhancing vaccine immunogenicity and laying the foundation for future, more solid data for its translation to the clinical practice.

Impact of Immunosenescence on Viral Infections with an Emphasis on COVID-19.

During aging, the immune system (IS) undergoes remarkable changes known as immunosenescence, a multifactorial and dynamic phenomenon that affects both natural and acquired immunity and plays an important role in most chronic diseases in older people. Among the determinants of immunosenescence, we find a low-grade sterile chronic inflammation, known as "inflamm-aging". This condition of chronic inflammation causes a progressive reduction in the ability to trigger antibody and cellular responses effective against infections and vaccinations. In this review, we wanted to explore the role of immunosenescence and inflamm-aging as determinants of the immunological aging process and predisposing viral infections phenomena, with a particular reference to cytomegalovirus (CMV), varicella zoster virus (VZV), influenza virus (IFV) diseases and SARS-CoV2. IS aging is also reflected in a reduction in the antibody response to vaccinations, hence there is a need to expand trials to elderly patients, in order to identify the most appropriate methods for developing effective and safe vaccination and preventive strategies.

Serologic immunogenicity and safety of Herpes Zoster subunit vaccine in patients with Rheumatoid Arthritis receiving Janus Kinase inhibitors.

OBJECTIVE: Patients with rheumatoid arthritis (RA) treated with Janus Kinase inhibitors (JAKi) are at increased risk of Herpes Zoster (HZ). The objective of this study was to investigate serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known. METHODS: RA patients treated with JAKi (n = 82) at the Department of Rheumatology, Skåne University Hospital, Sweden, and healthy controls (n = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect enzyme-linked immunosorbent assay (ELISA). Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed. RESULTS: Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (p< 0.0001). 80.5% of patients and 98.0% of controls achieved a ≥ 4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls (ratio 0.44, 95% CI 0.31-0.63), and lower in patients receiving JAKi+Methotrexate than JAKi monotherapy (ratio 0.43, 95% CI 0.24-0.79). AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination. CONCLUSION: The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for usage of the HZ/su vaccine in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03886038.

Early humoral and cellular responses after bivalent SARS-CoV-2 mRNA-1273.214 vaccination in long-term care and retirement home residents in Ontario, Canada: An observational cohort study.

Immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) bivalent mRNA-1273.214 vaccine (Original/Omicron B.1.1.529 [BA.1]) is underreported in vulnerable older adults in congregate care settings. In residents of 26 long-term care and retirement homes in Ontario, Canada, humoral (i.e., serum anti-spike and anti-receptor binding domain [anti-RBD]) IgG and IgA antibodies and live SARS-CoV-2 neutralization) and cellular (i.e., CD4+ and CD8+ activation-induced marker spike-specific T cell memory) responses were assessed 7-120 days postvaccination with four monovalent mRNA vaccines (n = 494) or subsequent bivalent mRNA-1273.214 vaccination (fifth vaccine) (n = 557). Within 4 months, anti-spike and anti-RBD antibody levels were similar after monovalent and bivalent vaccination in infection-naïve individuals. Hybrid immunity (i.e., vaccination and natural infection) generally increased humoral responses. After bivalent vaccination, compared to monovalent vaccination, residents with hybrid immunity had elevated anti-spike and anti-RBD IgG and IgA antibodies. Omicron BA.1 antibody-mediated neutralization, and CD8+ T cell memory responses to the Omicron BA.1 spike protein, were also higher after bivalent vaccination. Humoral and cellular responses were, therefore, noninferior within 4 months of bivalent mRNA-1273.214 vaccination compared to monovalent mRNA vaccination. Waning of humoral but not cellular immunity was particularly evident in individuals without hybrid immunity. Continued monitoring of vaccine-associated and hybrid immunity against emerging Omicron variants of concern is necessary to assess longevity of protection.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses.

Novavax, a global vaccine company, began evaluating NVX-CoV2373 in human studies in May 2020 and the pivotal placebo-controlled phase 3 studies started in November 2020; five clinical studies provided adult and adolescent clinical data for over 31,000 participants who were administered NVX-CoV2373. This extensive data has demonstrated a well-tolerated response to NVX-CoV2373 and high vaccine efficacy against mild, moderate, or severe COVID-19 using a two-dose series (Dunkle et al., 2022) [1], (Heath et al., 2021) [2], (Keech et al., 2020) [3], (Mallory et al., 2022) [4]. The most common adverse events seen after administration with NVX-CoV2373 were injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, nausea, or vomiting. In addition, immunogenicity against variants of interest (VOI) and variants of concern (VOC) was established with high titers of ACE2 receptor-inhibiting and neutralizing antibodies in these studies (EMA, 2022) [5], (FDA, 2023) [6]. Further studies on correlates of protection determined that titers of anti-Spike IgG and neutralizing antibodies correlated with efficacy against symptomatic COVID-19 established in clinical trials (p < 0.001 for recombinant protein vaccine and p = 0.005 for mRNA vaccines for IgG levels) (Fong et al., 2022) [7]. Administration of a booster dose of the recombinant protein vaccine approximately 6 months following the primary two-dose series resulted in substantial increases in humoral antibodies against both the prototype strain and all evaluated variants, similar to or higher than the antibody levels observed in phase 3 studies that were associated with high vaccine efficacy (Dunkle et al., 2022) [1], (Mallory et al., 2022) [4]. These findings, together with the well tolerated safety profile, support use of the recombinant protein vaccine as primary series and booster regimens.

The role of vaccination route with an adenovirus-vectored vaccine in protection, viral control, and transmission in the SARS-CoV-2/K18-hACE2 mouse infection model.

Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites. Methods: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival. Results: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed that animals vaccinated intranasally had improved cellular and mucosal antibody responses. Additionally, intranasally vaccinated animals had significantly better viremic control, and protection from lethal infection compared to intramuscularly vaccinated animals. Notably, in a novel transmission model, intranasal vaccination reduced viral transmission to naïve co-housed mice compared to intramuscular vaccination. Discussion: Our data provide convincing evidence for the use of intranasal vaccination in protecting against SARS-CoV-2 infection and transmission.

Trivalent inactivated influenza vaccine response and immunogenicity assessment after one week and three months in repeatedly vaccinated adults.

BACKGROUND: The influenza vaccine administrated every year is a recommended infection control procedure for individuals above the age of six months. However, the effectiveness of repeated annual vaccination is still an active research topic. Therefore, we investigated the vaccine immunogenicity in two independent groups: previously vaccinated versus non-vaccinated individuals at three time points; prior vaccination, one week and three months post vaccination. The assessment enabled us to evaluate the elicited immune responses and the durability of the induced protection in both groups. RESEARCH DESIGN AND METHODS: A research study was conducted to assess the immunogenicity of a single dose of Trivalent Inactivated Influenza Vaccine (A/H1N1, A/H3N2, and B) in 278 healthy adults aged between 32 and 66 years. Almost half of the participants, 140 (50·36%), received influenza vaccination at least once precursor to past influenza seasons. One blood sample was taken prior to vaccination for complete blood analysis and baseline immunogenicity assessment. The selected study participants received a single vaccine dose on the first day, and then followed up for three months. Two blood samples were taken after one week and three months post vaccination, respectively, for vaccine immunogenicity assessment. RESULTS: Before vaccination, the seroprotection, defined as a hemagglutination-inhibiting titer of =>1:40, was detected for the three vaccine virus strains in 20 previously vaccinated participants (14·29%) [8·95%, 21·2%]. We compared the overall vaccine response for the three virus strains using a normalized response score calculated from linearly transformed titer measurements; the score before vaccination was 84% higher in the previously vaccinated group and the mean difference between the two groups was statistically significant. Three months post-vaccination, we didn't find a significant difference in vaccine responses; the number of fully seroprotected individuals became 48 (34·29%) [26·48%, 42·77%] in the previously vaccinated group and 59 (42·75%) [34·37%, 51·45%] in the non-vaccinated group. The calculated response score was almost equal in both groups and the mean difference was no longer statistically significant. CONCLUSION: Our findings suggest that a single dose of influenza vaccine is equally protective after three months for annually vaccinated adults and first-time vaccine receivers.

Influence of SARS-CoV-2 mRNA Vaccine Booster among Cancer Patients on Active Treatment Previously Immunized with Inactivated versus mRNA Vaccines: A Prospective Cohort Study.

Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8-12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.

Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has significantly reduced the efficacy of some approved vaccines. A fourth dose of NVX-CoV2373 (5 µg SARS-CoV-2 recombinant spike [rS] protein + 50 µg Matrix-M™ adjuvant; Novavax, Gaithersburg, MD) was evaluated to determine induction of cross-reactive antibodies to variants of concern. A phase II randomized study (NCT04368988) recruited participants in Australia and the United States to assess a primary series of NVX-CoV2373 followed by two booster doses (third and fourth doses at 6-month intervals) in adults 18-84 years of age. The primary series was administered when the SARS-CoV-2 ancestral strain was prevalent and the third and fourth doses while the Alpha and Delta variants were prevalent in AUS and US. Local/systemic reactogenicity was assessed the day of vaccination and for 6 days thereafter. Unsolicited adverse events (AEs) were reported. Immunogenicity was measured before, and 14 days after, fourth dose administration, using anti-spike serum immunoglobulin G (IgG) and neutralization assays against ancestral SARS-CoV-2 strain and Omicron sublineages. Among 1283 enrolled participants, 258 were randomized to receive the two-dose primary series, of whom 104 received a third dose, and 45 received a fourth dose of NVX-CoV2373. The incidence of local/systemic reactogenicity events increased after the first three doses of NVX-CoV2373 and leveled off after dose 4. Unsolicited AEs were reported in 9 % of participants after dose 4 (none of which were severe or serious). Anti-rS IgG levels and neutralization antibody titers increased following booster doses to a level approximately four-fold higher than that observed after the primary series, with a progressively narrowed gap in response between the ancestral strain and Omicron BA.5. A fourth dose of NVX-CoV2373 enhanced immunogenicity for ancestral and variant SARS-CoV-2 strains without increasing reactogenicity, indicating that updates to the vaccine composition may not be currently warranted.

Immunogenicity and Safety of Homologous and Heterologous Prime-Boost of CoronaVac® and ChAdOx1 nCoV-19 among Hemodialysis Patients: An Observational Prospective Cohort Study.

BACKGROUND: Vaccines that prevent SARS-CoV-2 infection are considered the most promising approach to modulating the pandemic. There is scarce evidence on the efficacy and safety of different vaccine prime-boost combinations in MHD patients since most clinical trials have used homologous mRNA vaccine regimens. METHODS: This prospective observational study assessed the immunogenicity and safety of homologous CoronaVac® (SV-SV), ChAdOx1 nCoV-19 (AZD1222) (AZ-AZ), and the heterologous prime-boost of SV-AZ, among MHD patients. RESULTS: A total of 130 MHD participants were recruited. On day 28, after the second dose, seroconversion results of the surrogate virus neutralization test were not different between vaccine regimens. The magnitude of the receptor-binding domain-specific IgG was highest among the SV-AZ. Different vaccine regimens had a distinct impact on seroconversion, for which the heterologous vaccine regimen demonstrated a higher probability of seroconversion (OR 10.12; p = 0.020, and OR 1.81; p = 0.437 for SV-AZ vs. SV-SV, and SV-AZ vs. AZ-AZ, respectively). There were no serious adverse events reported in any of the vaccine groups. CONCLUSIONS: Immunization with SV-SV, AZ-AZ, and SV-AZ could generate humoral immunity without any serious adverse events among MHD patients. Using the heterologous vaccine prime-boost seemed to be more efficacious in terms of inducing immunogenicity.