Comparing Heterologous and Homologous COVID-19 Vaccination: A Longitudinal Study of Antibody Decay.

The humoral response after vaccination was evaluated in 1248 individuals who received different COVID-19 vaccine schedules. The study compared subjects primed with adenoviral ChAdOx1-S (ChAd) and boosted with BNT162b2 (BNT) mRNA vaccines (ChAd/BNT) to homologous dosing with BNT/BNT or ChAd/ChAd vaccines. Serum samples were collected at two, four and six months after vaccination, and anti-Spike IgG responses were determined. The heterologous vaccination induced a more robust immune response than the two homologous vaccinations. ChAd/BNT induced a stronger immune response than ChAd/ChAd at all time points, whereas the differences between ChAd/BNT and BNT/BNT decreased over time and were not significant at six months. Furthermore, the kinetic parameters associated with IgG decay were estimated by applying a first-order kinetics equation. ChAd/BNT vaccination was associated with the longest time of anti-S IgG negativization and with a slow decay of the titer over time. Finally, analyzing factors influencing the immune response by ANCOVA analysis, it was found that the vaccine schedule had a significant impact on both the IgG titer and kinetic parameters, and having a Body Mass Index (BMI) above the overweight threshold was associated with an impaired immune response. Overall, the heterologous ChAd/BNT vaccination may offer longer-lasting protection against SARS-CoV-2 than homologous vaccination strategies.

Long-Term Cross Immune Response in Mice following Heterologous Prime-Boost COVID-19 Vaccination with Full-Length Spike mRNA and Recombinant S1 Protein.

(1) Background: As the COVID-19 pandemic enters its fourth year, it continues to cause significant morbidity and mortality worldwide. Although various vaccines have been approved and the use of homologous or heterologous boost doses is widely promoted, the impact of vaccine antigen basis, forms, dosages, and administration routes on the duration and spectrum of vaccine-induced immunity against variants remains incompletely understood. (2) Methods: In this study, we investigated the effects of combining a full-length spike mRNA vaccine with a recombinant S1 protein vaccine, using intradermal/intramuscular, homologous/heterologous, and high/low dosage immunization strategies. (3) Results: Over a period of seven months, vaccination with a mutant recombinant S1 protein vaccine based on the full-length spike mRNA vaccine maintained a broadly stable humoral immunity against the wild-type strain, a partially attenuated but broader-spectrum immunity against variant strains, and a comparable level of cellular immunity across all tested strains. Furthermore, intradermal vaccination enhanced the heterologous boosting of the protein vaccine based on the mRNA vaccine. (4) Conclusions: This study provides valuable insights into optimizing vaccination strategies to address the ongoing challenges posed by emerging SARS-CoV-2 variants.

Omicron infection-associated T- and B-cell immunity in antigen-naive and triple-COVID-19-vaccinated individuals.

Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2-3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigen-naive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus.

COVID-19: Delphi analysis for the evaluation of the transition from pandemic to endemic in Mexico.

OBJECTIVE: To review and analyze the available information about the COVID-19 pandemic in Mexico and the determining factors for its transition to an endemic phase. MATERIALS AND METHODS: Prospective study based on the Delphi Method with the participation of a panel made up by specialists in infectious diseases, immunology, internal medicine, pulmonology, pediatrics and public health. RESULT(S): 2270 bibliographic sources were identified;after excluding those that offered repetitive information, 454 were included in the final analysis. The main factors that obstruct the transition from a COVID-19 pandemic to an endemic one were defined as the high capacity of SARS-CoV-2 to mutate (since the efficacy of anti-COVID-19 vaccines depends to a large extent on the genetic presentations of the virus) and the high prevalence in the country of comorbidities that make the population more vulnerable against the disease. Strengthening primary care and promoting a culture of surveillance and prevention are essential. CONCLUSION(S): It was concluded, by consensus, that there are factors that obstruct the passage of the COVID-19 pandemic to an endemic phase, including the intrinsic nature of disease control and the unpredictability of virus mutations.Copyright © 2023 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

Evaluation of Side Effects After Heterologous Vaccination with BNT162b2 Vaccine in Healthcare Workers Vaccinated with Two Doses of Inactive COVID-19 Vaccine

Objective: Vaccination is the most effective way to control the COVID-19 pandemic all over the world. We aimed to evaluate the relationship between antibody titers and vaccine side effects after the BNT162b2 vaccine was administered as a reminder dose in healthcare workers (HCW) who received two doses of inactivated SARS-CoV-2 vaccine name CoronaVac (Sinovac Life Sciences, Beijing, China).Methods: A total of 428 HCWs participated in the study. Participants who received the mRNA vaccine as a reminder dose were evaluated with a questionnaire regarding antibody values and vaccine side effects. Three weeks after the first BNT162b2 vaccine, the same questionnaire was applied face-to-face to HCW, and the same questionnaire was applied to those who received a second reminder dose via telephone.Results: Out of 428, 373 (87.1%) HCWs preferred one and 55 (12.9%) two doses of the BNT162b2 vaccine as reminder doses after being vaccinated with an inactivated vaccine. It was observed that side effects were more frequent in women aged 18-40 after a single dose of the BNT162b2 vaccine (p<0.001). The most common side effects are redness, swelling, and pain at the injection site, with a rate of 59.6%. Fatigue-weakness was the most common systemic reaction, with a rate of 58.6%. Axillary lymphadenopathy was observed seen in 3 (1.1%) HCWs. The median value of IgG titers in the third week after the reminder dose was found to be higher in HCW with side effects than those without side effects (p<0.001). When the cumulative incidence rate of vaccinated people was evaluated over 389 people, no cases were ob-served on the 14th and 30th days after the first reminder dose of BNT162b2. However, the first case was observed on the 60th day, and after the second reminder dose, cases were seen on the 14th, 30th, and 60th days.Conclusion: Since the side effects detected after the BNT162b2 reminder dose were mild to moderate and progressed with local symptoms, it was concluded that highly protective mRNA vaccines could be safely preferred for protection from COVID-19.

BOOSTER VACCINATION AGAINST SARS-CoV-2: CURRENT CHALLENGES AND SOLUTIONS.

The COVID-19 pandemic is going on, which makes it crucial to prevent the spread of coronavirus disease. Vaccination is the only way of specific prevention of COVID-19. The SARS-CoV-2 virus is continuously evolving and new variants appear. Moreover, the effectiveness of protective immunity after vaccination tends to decrease over several months. Booster vaccination may be the solution to these problems. The booster is an extra vaccination that helps to reactivate the immunity against COVID-19. Booster doses can be homologous (the same as the primary vaccine) and heterologous (different from the primary vaccine). It is of current interest to study heterologous vaccination as the injection of different vaccines may result in a more intense immune response. Furthermore, the same vaccine may not be available at the time of booster vaccination. This review is aimed at summarizing the key research findings in the field of booster vaccination against COVID-19.Copyright © 2022 Booster vaccination against. All rights reserved.

Safety and immunogenicity of heterologous ChAdOx1-nCoV19 and BNT162b2 vaccination: A meta-analysis of the heterologous COVID-19 vaccination outcomes.

INTRODUCTION: Here, we systematically assessed the safety and immunogenicity of the heterologous ChAd/BNT vaccination regimens. MATERIALS AND METHODS: We evaluated the immunogenicity by the geometric mean titers ratio (GMTR) of the neutralizing antibody and anti-spike IgG. The safety of heterologous ChAd/BNT vaccination was evaluated using the pooled risk ratios (RRs) calculated by the random-effects model about the adverse events. Our study was registered with PROSPERO, CRD42021265165. RESULTS: Eleven studies were included in the analyses. Compared to the homologous ChAd/ChAd vaccination, the heterologous ChAd/BNT vaccination showed significantly higher immunogenicity in terms of the neutralizing antibody and GMTR of anti-spike IgG, but at the same time displayed higher incidence of total adverse reactions, especially for the local adverse reactions. Moreover, heterologous ChAd/BNT vaccination showed similar immunogenicity to the homologous BNT/BNT vaccination (GMTR of neutralizing antibody and anti-spike IgG) and similar safety. DISCUSSION: Heterologous ChAd/BNT vaccination showed robust immunogenicity and tolerable safety.

Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity.

Currently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4+ T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development.

Humoral Immune Response of Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Prime-Boost Vaccination against SARS-CoV-2 Variants in Korea.

The immunogenicity of a heterologous vaccination regimen consisting of ChAdOx1 nCoV-19 (a chimpanzee adenovirus-vectored vaccine) followed by mRNA-1273 (a lipid-nanoparticle-encapsulated mRNA-based vaccine) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), specifically the omicron variant (B.1.1.529), is poorly studied. The aim of this study was to evaluate the neutralizing antibody activity and immunogenicity of heterologous ChAdOx1 nCoV-19 and mRNA-1273 prime-boost vaccination against wild-type (BetaCoV/Korea/KCDC03/2020), alpha, beta, gamma, delta, and omicron variants of SARS-CoV-2 in Korea. A 50% neutralizing dilution (ND50) titer was determined in serum samples using the plaque reduction neutralization test. Antibody titer decreased significantly at 3 months compared with that at 2 weeks after the 2nd dose. On comparing the ND50 titers for the above-mentioned variants of concerns, it was observed that the ND50 titer for the omicron variant was the lowest. This study provides insights into cross-vaccination effects and can be useful for further vaccination strategies in Korea.

Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5-included SARS-CoV-2 variants than homologous vaccination of mRNA vaccine.

BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild-type SARS-CoV-2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full-length spike protein sequence-based mRNA vaccine as the "priming" shot and developed a recombinant trimeric receptor-binding domain (RBD) protein vaccine referred to as RBD-HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD-HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5-included SARS-CoV-2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long-lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD-HR/trimer following two-dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD-HR/trimer vaccine becomes an appropriate candidate for a booster immune injection.

Anti-SARS-CoV-2 spike IgG following injection of the third dose vaccine: A systematic review with meta-analysis of heterologous versus homologous vaccination.

Background: The mass vaccination is a key strategy to prevent and control the coronavirus disease 2019 (COVID-19) pandemic. Today, several different types of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed worldwide. These vaccines are usually administered in a two-dose schedule, and the third dose is currently being administered in most countries. This study aimed to systematically review and meta-analyze the immunogenicity of heterologous vs. homologous vaccination after administration of the third dose of COVID-19 vaccines. Methods: Electronic databases and websites including Scopus, PubMed, Web of Science, and Google scholar were searched for relevant randomized clinical trial (RCT) studies. After applying the inclusion and exclusion criteria, a total of three RCTs were included in the study. These RCTs were included 2,613 healthy adults (18 years or older and without a history of laboratory-confirmed COVID-19) with 15 heterologous and five homologous prime-boost vaccination regimens. Anti-SARS-CoV-2-spike IgG levels at day 28 after administration of the third dose, were compared between the heterologous and homologous regimens. Results: The highest antibody responses had been reported for the homologous vaccination regimen of m1273/m1273/m1273 (Moderna), followed by the heterologous regimen of BNT/BNT/m1273. In addition, the immunogenicity of viral vector and inactivated vaccines was remarkably enhanced when they had been boosted by a heterologous vaccine, especially mRNA vaccines. Conclusion: This systematic review suggests that mRNA vaccines in a homologous regimen induce strong antibody responses to SARS-CoV-2 compared to other vaccine platforms. In contrast, viral vector and inactivated vaccines show a satisfactory immunogenicity in a heterologous regimen, especially in combination with mRNA vaccines.

Evaluation of Side Effects After Heterologous Vaccination with BNT162b2 Vaccine in Healthcare Workers Vaccinated with Two Doses of Inactive COVID-19 Vaccine.

Objective: Vaccination is the most effective way to control the COVID-19 pandemic all over the world. We aimed to evaluate the relationship between antibody titers and vaccine side effects after the BNT162b2 vaccine was administered as a reminder dose in healthcare workers (HCW) who received two doses of inactivated SARS-CoV-2 vaccine name CoronaVac (Sinovac Life Sciences, Beijing, China). Method(s): A total of 428 HCWs participated in the study. Participants who received the mRNA vaccine as a reminder dose were evaluated with a questionnaire regarding antibody values and vaccine side effects. Three weeks after the first BNT162b2 vaccine, the same questionnaire was applied face-to-face to HCW, and the same questionnaire was applied to those who received a second reminder dose via telephone. Result(s): Out of 428, 373 (87.1%) HCWs preferred one and 55 (12.9%) two doses of the BNT162b2 vaccine as reminder doses after being vaccinated with an inactivated vaccine. It was observed that side effects were more frequent in women aged 18-40 after a single dose of the BNT162b2 vaccine (p<0.001). The most common side effects are redness, swelling, and pain at the injection site, with a rate of 59.6%. Fatigue-weakness was the most common systemic reaction, with a rate of 58.6%. Axillary lymphadenopathy was observed seen in 3 (1.1%) HCWs. The median value of IgG titers in the third week after the reminder dose was found to be higher in HCW with side effects than those without side effects (p<0.001). When the cumulative incidence rate of vaccinated people was evaluated over 389 people, no cases were observed on the 14th and 30th days after the first reminder dose of BNT162b2. However, the first case was observed on the 60th day, and after the second reminder dose, cases were seen on the 14th, 30th, and 60th days. Conclusion(s): Since the side effects detected after the BNT162b2 reminder dose were mild to moderate and progressed with local symptoms, it was concluded that highly protective mRNA vaccines could be safely preferred for protection from COVID-19. Copyright © 2022, DOC Design and Informatics Co. Ltd.. All rights reserved.

A heterologous AZD1222 priming and BNT162b2 boosting regimen more efficiently elicits neutralizing antibodies, but not memory T cells, than the homologous BNT162b2 regimen.

BACKGROUND: Comparative analyses of SARS-CoV-2-specific immune responses elicited by diverse prime-boost regimens are required to establish efficient regimens for the control of COVID-19. METHOD: In this prospective observational cohort study, spike-specific immunoglobulin G (IgG) and neutralizing antibodies (nAbs) alongside spike-specific T-cell responses in age-matched groups of homologous BNT162b2/BNT162b2 or AZD1222/AZD1222 vaccination, heterologous AZD1222/BNT162b2 vaccination, and prior wild-type SARS-CoV-2 infection/vaccination were evaluated. RESULTS: Peak immune responses were achieved after the second vaccine dose in the naïve vaccinated groups and after the first dose in the prior infection/vaccination group. Peak titers of anti-spike IgG and nAb were significantly higher in the AZD1222/BNT162b2 vaccination and prior infection/vaccination groups than in the BNT162b2/BNT162b2 or AZD1222/AZD1222 groups. However, the frequency of interferon-γ-producing CD4+ T cells was highest in the BNT162b2/BNT162b2 vaccination group. Similar results were observed in the analysis of polyfunctional T cells. When nAb and CD4+T-cell responses against the Delta variant were analyzed, the prior infection/vaccination group exhibited higher responses than the groups of other homologous or heterologous vaccination regimens. CONCLUSION: nAbs are efficiently elicited by heterologous AZD1222/BNT162b2 vaccination, as well as prior infection/vaccination, whereas spike-specific CD4+T-cell responses are efficiently elicited by homologous BNT162b2 vaccination. Variant-recognizing immunity is more efficiently generated by prior infection/vaccination than the other homologous or heterologous vaccination regimens.

Evaluation of Side Effects After Heterologous Vaccination with BNT162b2 Vaccine in Healthcare Workers Vaccinated with Two Doses of Inactive COVID-19 Vaccine

Objective: Vaccination is the most effective way to control the COVID-19 pandemic all over the world. We aimed to evaluate the relationship between antibody titers and vaccine side effects after the BNT162b2 vaccine was administered as a reminder dose in healthcare workers (HCW) who received two doses of inactivated SARS-CoV-2 vaccine name CoronaVac (Sinovac Life Sciences, Beijing, China). Method(s): A total of 428 HCWs participated in the study. Participants who received the mRNA vaccine as a reminder dose were evaluated with a questionnaire regarding antibody values and vaccine side effects. Three weeks after the first BNT162b2 vaccine, the same questionnaire was applied face-to-face to HCW, and the same questionnaire was applied to those who received a second reminder dose via telephone. Result(s): Out of 428, 373 (87.1%) HCWs preferred one and 55 (12.9%) two doses of the BNT162b2 vaccine as reminder doses after being vaccinated with an inactivated vaccine. It was observed that side effects were more frequent in women aged 18-40 after a single dose of the BNT162b2 vaccine (p<0.001). The most common side effects are redness, swelling, and pain at the injection site, with a rate of 59.6%. Fatigue-weakness was the most common systemic reaction, with a rate of 58.6%. Axillary lymphadenopathy was observed seen in 3 (1.1%) HCWs. The median value of IgG titers in the third week after the reminder dose was found to be higher in HCW with side effects than those without side effects (p<0.001). When the cumulative incidence rate of vaccinated people was evaluated over 389 people, no cases were observed on the 14th and 30th days after the first reminder dose of BNT162b2. However, the first case was observed on the 60th day, and after the second reminder dose, cases were seen on the 14th, 30th, and 60th days. Conclusion(s): Since the side effects detected after the BNT162b2 reminder dose were mild to moderate and progressed with local symptoms, it was concluded that highly protective mRNA vaccines could be safely preferred for protection from COVID-19. Copyright © 2022, DOC Design and Informatics Co. Ltd.. All rights reserved.

No changes in hemostasis after COVID-19-heterologous vaccination schedule: A subanalysis of the phase 2 CombiVacS study.

Background: Several cases of unusual thrombotic events and thrombocytopenia were described after vaccination with recombinant adenoviral vectors encoding the spike protein antigen of SARS-CoV-2. Objectives: The objective of this study was to elucidate the impact of a COVID-19 heterologous vaccination schedule, including priming with adenovirus vaccine, on hemostasis profiles. Methods: The present study is a subanalysis of the CombiVacS clinical trial initiated in April 2021 that included adult participants previously vaccinated with a single dose of ChAdOx1-S. Between 8 and 12 weeks after vaccination, they were randomly assigned (2:1) to receive either BNT162b2 vaccine (intervention group, n = 99) or continue observation (control group, n = 50). Samples drawn before and 28 days after a vaccination with BNT162b2 were analyzed for platelet count and markers of hemostasis (D-dimer, anti-PF4 antibodies, cfDNA, PAI-1, thrombin generation, and serum capacity to activate platelets). Results: Platelet count from all participants after receiving BNT162b2 was within the normal range. Anti-PF4 antibodies were present in 26% and 18% of the subjects from the control and intervention groups, respectively, at day 28. In most cases, the levels of anti-PF4 antibodies were high before receiving BNT162b2. Serum from these participants did not activate platelets from healthy controls. There were no differences between the groups in PAI-1 and cfDNA plasma levels. According to the D-dimer plasma concentration, the thrombin generation test showed that none of the participants had a procoagulant profile. Conclusion: Our data suggest that the heterologous vaccination against COVID-19 with ChAdOx1-S and a second dose with BNT162b2 might be safe in terms of haemostasis.

Willingness of college students to receive COVID-19 heterologous vaccination in Taizhou, China.

This study aimed to determine the willingness of college students to choose COVID-19 heterologous vaccination and its associated influencing factors in Taizhou, China. A population-based, self-administered online questionnaire was conducted from March 15 to 17, 2022. Of the 2,463 participants who had received the invitation, 1,821 responded to the survey (response rate = 73.9%). Only 14% (86/614) of those willing to receive a booster would chose a heterologous vaccination; the perception of better effectiveness of a COVID-19 heterologous vaccination booster was the significant factor (X2 = 22.671, p < .001). Additionally, female college students'older age (χ2 = 7.523, P = .023), major of medical (χ2 = 6.294, P = .012), and better perceived effectiveness of COVID-19 heterologous vaccination booster (χ2 = 22.659, P < .001), were more willing to receive heterologous booster doses. Chinese college students have a strong willingness to receive booster shots, but the percentage of those willing to receive a heterologous vaccine is only 14.0%, and the lack of understanding of its effectiveness is an important factor in the low proportion of heterologous vaccine selection. Health education, public health awareness, and the disclosure of heterologous vaccine information can help improve the public's understanding of heterologous vaccines and provide them with more choices.

COVID-19 in kidney transplantation-implications for immunosuppression and vaccination.

COVID-19 pandemic continues to challenge the transplant community, given increased morbidity and mortality associated with the disease and poor response to prevention measures such as vaccination. Transplant recipients have a diminished response to both mRNA and vector-based vaccines compared to dialysis and the general population. The currently available assays to measure response to vaccination includes commercially available antibody assays for anti-Spike Ab, or anti- Receptor Binding Domain Ab. Positive antibody testing on the assays does not always correlate with neutralizing antibodies unless the antibody levels are high. Vaccinations help with boosting polyfunctional CD4+ T cell response, which continues to improve with subsequent booster doses. Ongoing efforts to improve vaccine response by using additional booster doses and heterologous vaccine combinations are underway. There is improved antibody response in moderate responders; however, the ones with poor response to initial vaccination doses, continue to have a poor response to sequential boosters. Factors associated with poor vaccine response include diabetes, older age, specific immunosuppressants such as belatacept, and high dose mycophenolate. In poor responders, a decrease in immunosuppression can increase response to vaccination. COVID infection or vaccination has not been associated with an increased risk of rejection. Pre- and Post-exposure monoclonal antibodies are available to provide further protection against COVID infection, especially in poor vaccine responders. However, the efficacy is challenged by the emergence of new viral strains. A recently approved bivalent vaccine offers better protection against the Omicron variant.

Regimen of Coronavirus Disease 2019 Vaccination Influences Extent and Kinetics of Antibody Avidity.

We investigated antibody titers and avidity after heterologous versus homologous coronavirus disease 2019 vaccination over 6 months after the second dose. We found a significantly higher avidity in regimens including at least 1 dose of the adenoviral vector vaccine ChAdOx1-S compared with 2 doses of the mRNA vaccine BNT162b2.

Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2.

BACKGROUND: Vaccines are an important means to overcome the SARS-CoV-2 pandemic. They induce specific antibody and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 180 days after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both. METHODS: Various tests were used to determine the humoral and cellular immune response. To quantify the antibody levels, we used the surrogate neutralization (sVNT) assay from YHLO, which we augmented with pseudo- and real virus neutralization tests (pVNT and rVNT). Antibody avidity was measured by a modified ELISA. To determine cellular reactivity, we used an IFN-γ Elispot, IFN-γ/IL Flurospot, and intracellular cytokine staining. FINDINGS: Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV-2 - including variants of concern such as Delta or Omicron - was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homologous ChAd immunization. All vaccination regimens induced stable, polyfunctional T-cell responses. INTERPRETATION: These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent alternative to induce humoral and cellular immune protection in comparison to the homologous vaccination regimens. FUNDING: The study was funded by the German Centre for Infection Research (DZIF), the European Union's "Horizon 2020 Research and Innovation Programme" under grant agreement No. 101037867 (VACCELERATE), the "Bayerisches Staatsministerium für Wissenschaft und Kunst" for the CoVaKo-2021 and the For-COVID projects and the Helmholtz Association via the collaborative research program "CoViPa". Further support was obtained from the Federal Ministry of Education and Science (BMBF) through the "Netzwerk Universitätsmedizin", project "B-Fast" and "Cov-Immune". KS is supported by the German Federal Ministry of Education and Research (BMBF, 01KI2013) and the Else Kröner-Stiftung (2020_EKEA.127).

Reactogenicity and Humoral Immune Response after Heterologous Vaxzevria/Comirnaty Vaccination in a Group of Individuals Vaccinated in the AOU Policlinic "G. Martino" (Messina, Italy): A Retrospective Cohort Study.

On 11 June 2021, the Italian Ministry of Health authorized the heterologous vaccination schedule. The goals of our retrospective study were to (a) evaluate the undesirable effects after the administration of Vaxzevria and Comirnaty vaccines; (b) evaluate the antibody response after 28 days from the administration of the second dose; and (c) compare the antibody responses after the homologous and heterologous vaccination regimens. The undesirable effects were collected using a survey; IgG Spike was quantified using the electrochemiluminescence method; the comparison between the antibody responses was carried out using the sample of a homologous vaccine schedule previously analyzed. Pain at the injection site is the most common undesirable effect after the administration of both vaccines (62.1% after Vaxzevria vs. 82.75% after Comirnaty); swelling at the injection site is more frequent after the administration of Vaxzevria than after the administration of Comirnaty: (15.52% vs. 5.17%); headache is more frequent in women than in men for both the vaccination types (p < 0.05); 49.09% of the sample reported IgG Spike ≥ 12,500 U/mL; the antibody titer of the heterologous schedule is higher than that of the homologous vaccination. Our study demonstrated that the undesirable effects after the administration of the second dose are less frequent and less severe than after the administration of the first dose, and that the immunogenicity of the heterologous vaccinations is higher than that of the homologous ones.