A third COVID-19 vaccine shot markedly boosts neutralizing antibody potency and breadth

COVID-19 (coronavirus disease 2019) vaccines have been rapidly developed and deployed globally as a measure to combat the disease. These vaccines have been demonstrated to confer significant protection, but there have been reports of temporal decay in antibody titer. Furthermore, several variants have been identified with variable degrees of antibody resistance. These two factors suggest that a booster vaccination may be worthy of consideration. While such a booster dose has been studied as a series of three homologous vaccines in healthy individuals, to our knowledge, information on a heterologous regimen remains unreported, despite the practical benefits of such a scheme. Here, in this observational study, we investigated the serological profile of four healthy individuals who received two doses of the BNT162b2 vaccine, followed by a third booster dose with the Ad26.COV2.S vaccine. We found that while all individuals had spike-binding antibodies at each of the timepoints tested, there was an appreciable drop in titer by four months following the second vaccination. The third vaccine dose robustly increased titers beyond that of two vaccinations, and these elicited antibodies had neutralizing capability against all SARS-CoV-2 strains tested in both a recombinant vesicular stomatitis virus-based pseudovirus assay and an authentic SARS-CoV-2 assay, except for one individual against B.1.351 in the latter assay. Thus, a third COVID-19 vaccine dose in healthy individuals promoted not just neutralizing antibody potency, but also induced breadth against dominant SARS-CoV-2 variants.

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Rapid induction of antigen-specific CD4+ T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination

10.1101/2021.04.21.440862 ◽

2021 ◽

Author(s):

Mark M. Painter ◽

Divij Mathew ◽

Rishi R. Goel ◽

Sokratis A. Apostolidis ◽

Ajinkya Pattekar ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Natural Infection ◽

Vaccine Dose ◽

Booster Vaccination ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Integrated Analysis ◽

Cell Responses ◽

Rapid Induction

SummaryThe SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses in healthy individuals following mRNA vaccination. Vaccination induced rapid near-maximal antigen-specific CD4+ T cell responses in all subjects after the first vaccine dose. CD8+ T cell responses developed gradually after the first and second dose and were variable. Vaccine-induced T cells had central memory characteristics and included both Tfh and Th1 subsets, similar to natural infection. Th1 and Tfh responses following the first dose predicted post-boost CD8+ T cell and neutralizing antibody levels, respectively. Integrated analysis of 26 antigen-specific T cell and humoral responses revealed coordinated features of the immune response to vaccination. Lastly, whereas booster vaccination improved CD4+ and CD8+ T cell responses in SARS-CoV-2 naïve subjects, the second vaccine dose had little effect on T cell responses in SARS-CoV-2 recovered individuals. Thus, longitudinal analysis revealed robust T cell responses to mRNA vaccination and highlighted early induction of antigen-specific CD4+ T cells.Graphical Abstract

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Sequential immunization with SARS-CoV-2 RBD vaccine induces potent and broad neutralization against variants in mice

Virology Journal ◽

10.1186/s12985-021-01737-3 ◽

2022 ◽

Vol 19 (1) ◽

Author(s):

Shuo Song ◽

Bing Zhou ◽

Lin Cheng ◽

Weilong Liu ◽

Qing Fan ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Booster Dose ◽

Booster Vaccination ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Inactivated Vaccine ◽

Wild Type ◽

Broadly Neutralizing Antibodies ◽

Vaccination Strategies ◽

Inactivated Vaccines

AbstractThe current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.

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mRNA Booster Vaccines Elicit Strong Protection Against SARS-CoV-2 Omicron Variant in Cancer Patients

10.1101/2021.12.28.21268398 ◽

2021 ◽

Author(s):

Cong Zeng ◽

John P. Evans ◽

Karthik Chakravarthy ◽

Panke Qu ◽

Sarah Reisinger ◽

...

Keyword(s):

Public Health ◽

Cancer Patients ◽

Vaccine Dose ◽

Booster Vaccination ◽

Neutralizing Antibody ◽

Healthy Adults ◽

Global Public Health ◽

Health Concerns ◽

Vaccination Strategies

Following its emergence in late November of 2020, the SARS-CoV-2 Omicron (B.1.1.529) variant has caused major global public health concerns. We recently demonstrated that in healthy adults the Omicron variant exhibits strong resistance to immunity induced by two doses of the mRNA vaccines, but a booster mRNA vaccine dose can provide strong protection against Omicron. However, it is currently unknown how well these mRNA vaccine boosters protect immunocompromised groups, including cancer patients, from the Omicron variant. Here we show that (1) neutralizing antibody (nAb) titers against the Delta and Omicron variants in cancer patients after two-dose mRNA vaccines are 4.2-fold and 21.3-fold lower, respectively, compared to the ancestral D614G, and (2) nAb titers against the Delta and Omicron variants in boosted cancer patients are 3.6-fold and 5.1-fold lower, respectively, compared to D614G. Our findings highlight the effectiveness and need for booster vaccination strategies in immunocompromised groups including cancer patients to protect from the Omicron variant.

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Third COVID-19 Vaccine Dose Boosts Neutralizing Antibodies in Poor Responders

10.21203/rs.3.rs-1168060/v1 ◽

2021 ◽

Author(s):

Douglas Lake ◽

Alexa Roeder ◽

Maria Gonzalez-Moa ◽

Megan Koehler ◽

Erin Kaleta ◽

...

Keyword(s):

High Risk ◽

Neutralizing Antibodies ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Fold Increase ◽

Poor Responders ◽

Healthy Individuals ◽

Vaccine Responses ◽

Rna Vaccine

Abstract Background While evaluating COVID-19 vaccine responses using a rapid neutralizing antibody (NAb) test, we observed that 25% of RNA vaccine recipients did not neutralize >50%. We termed this group “vaccine poor responders” (VPRs). The objective of this study was to determine if individuals who neutralized <50% would remain VPRs, or if a third dose would elicit high levels of NAbs. Methods 269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA1273 (Moderna) vaccines were evaluated. NAb levels were measured: i) 2-4 weeks after a second vaccine dose, ii) 2-4 months after the second dose, iii) within 1-2 weeks prior to a third dose and iv) 2-4 weeks after a third RNA vaccine dose. Results Analysis of vaccine recipients revealed that 25% did not neutralize above 50% (Median neutralization = 21%, titers <1:80) within a month after their second dose. Twenty-three of these VPRs obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1-8 months (average = 5 months) after their second dose. Within a month after their third dose, VPRs showed an average 20-fold increase in NAb levels (range: 46%-99%). Conclusions The results suggest that VPRs are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose. Although it is not known what levels of NAbs protect from infection or disease, those in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, and potential transmission.

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Antibody response to immunization with influenza A/USSR/77 (H1N1) virus in young individuals primed or unprimed for A/New Jersey/76 (H1N1) virus

Journal of Hygiene ◽

10.1017/s0022172400069412 ◽

1981 ◽

Vol 87 (2) ◽

pp. 201-209 ◽

Cited By ~ 59

Author(s):

N. Masurel ◽

P. Ophof ◽

P. de Jong

Keyword(s):

New Jersey ◽

Side Effects ◽

Antibody Response ◽

Virus Vaccine ◽

Influenza A ◽

H1n1 Virus ◽

Vaccine Dose ◽

Booster Vaccination ◽

Booster Immunization ◽

Group A

SummaryA group of 269 pupils of the Harbour and Transport Training Institute in Rotterdam (group A), aged 13–20 years, and of 109 patients of the Dr Mr Willem van den Bergh Foundation at Noordwijk (group B), aged 11–21 years, were immunized with a whole virus vaccine containing 10, 20, or 40 μg HA of A/USSR/92/77 (H1N1) influenza virus. A booster vaccination was administered 6 weeks later with 20 μg HA of the same virus. Many of the participants had been immunized during the two preceding years with a whole virus vaccine containing A/New Jersey/8/76 (H1N1) (A/NJ/76) virus. The side-effects, mostly of a moderate nature, increased with the dose of virus in the vaccine. In group A side effects were least frequent in the vaccinees who had never received A/NJ/76 vaccine. A single dose of A/USSR/77 vaccine did not produce satisfactory levels of homologous antibodies. After booster immunization with 20 μg HA of A/USSR/77 virus participants showed a higher homologous antibody response in all vaccine-dose groups if they had not been immunized with A/NJ/76 virus in previous years. After primary and especially after booster immunization with A/USSR/77 virus, a very high response against A/NJ/76 virus and adequate levels of A/NJ/76 antibody were found in participants who had been immunized previously with A/NJ/76 virus. Those who had not been immunized with this virus previously showed no or a very low antibody response to A/NJ/76 virus.

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Serological response to rabies virus induced by commercial vaccines in cattle

Ciência Rural ◽

10.1590/0103-8478cr20161044 ◽

2017 ◽

Vol 47 (10) ◽

Author(s):

Mathias Martins ◽

João Motta de Quadros ◽

Eduardo Furtado Flores ◽

Rudi Weiblen

Keyword(s):

Rabies Virus ◽

Neutralizing Antibodies ◽

Vaccine Dose ◽

Booster Vaccination ◽

Serological Response ◽

Serum Samples ◽

Anamnestic Response ◽

Post Vaccination ◽

Antibody Titers ◽

One Year

ABSTRACT: The antibody response to rabies virus (RABV) induced by commercial vaccines in heifers was investigated. For this, 84 heifers were vaccinated twice (30 days interval) with each of four vaccines (G1 = 14 animals; G2 = 24; G3 = 22 and G4 = 24) and received a booster vaccination 360 days later. Serum samples collected at different intervals after vaccination and 30 days after booster were submitted to a virus neutralizing (VN) assay for RABV antibodies. Thirty days after the second vaccine dose, 92% of the immunized animals presented VN titers ≥0.5UI/mL (geometric medium titers [GMT] 1.7 to 3.8UI/mL). At the day of the booster (360 days post-vaccination); however, the percentage of animals harboring antibody titers ≥0.5UI/mL had dropped to 31% (0-80% of the animals, depending on the vaccine), resulting in lower GMT (0.1 to 0.6UI/mL). Booster vaccination at day 360 resulted in a detectable anamnestic response in all groups, resulting in 83% of animals (65 to 100%) harboring VN titers ≥0.5UI/mL thirty days later (GMT 0.6 to 4.3UI/mL). These results indicated that these vaccines were able to induce an adequate anti-RABV response in all animals after prime vaccination (and after booster as well). However, the titers decreased, reaching titers <0.5UI/mL in approximately 70% of animals within the interval before the recommended booster. Thus, booster vaccination for rabies in cattle using the current vaccines should be performed before the recommended one-year interval, as to maintain neutralizing antibodies levels in most vaccinated animals.

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Durability of Response to a Third BNT162b2 Vaccine in Adults ≥60 Years

10.1101/2021.12.25.21268336 ◽

2021 ◽

Author(s):

Noa Eliakim Raz ◽

Amos Stemmer ◽

Yaara Leibovici-Weissman ◽

Asaf Ness ◽

Muhammad Awwad ◽

...

Keyword(s):

Adverse Events ◽

Neutralizing Antibodies ◽

Multivariable Analysis ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Clinical Frailty Scale ◽

Younger Adults ◽

The Third ◽

Antibody Titers ◽

Level 2

BACKGROUND Age and frailty are strong predictors of COVID-19 mortality. After the second BNT162b2 dose, immunity wanes faster in older (≥65 years) versus younger adults. The durability of response after the third vaccine is unclear. METHODS This prospective cohort study included healthcare workers/family members ≥60 years who received a third BNT162b2 dose. Blood samples were drawn immediately before (T0), 10-19 (T1), and 74-103 (T2) days after the third dose. Antispike IgG titers were determined using a commercial assay, seropositivity was defined as ≥50 AU/mL. Neutralizing antibody titers were determined at T2. Adverse events, COVID-19 infections, and clinical frailty scale (CFS) levels were documented. RESULTS The analysis included 97 participants (median age, 70 years [IQR, 66-74], 61% women, 58% CFS level 2). IgG titers, which increased significantly from T0 to T1 (medians, 440 AU/mL [IQR, 294-923] and 25,429 [14,203-36,114] AU/mL, respectively; P<0.001), decreased significantly by T2, but all remained seropositive (median, 8,306 AU/mL [IQR, 4595-14,701], P<0.001 vs T1). In a multivariable analysis, only time from the first vaccine was significantly associated with lower IgG levels at T2 (P=0.004). At T2, 60 patients were evaluated for neutralizing antibodies; all were seropositive (median, 1,294 antibody titer [IQR, 848-2,072]). Neutralizing antibody and antispike IgG levels were correlated (R=0.6, P<0.001). No major adverse events or COVID-19 infections were reported. CONCLUSIONS Antispike IgG and neutralizing antibodies levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults ≥60 years, although the decline in IgG is concerning. A third vaccine dose in this population should be top priority.

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Self-reported and physiological reactions to the third BNT162b2 mRNA COVID-19 (booster) vaccine dose

10.1101/2021.09.15.21263633 ◽

2021 ◽

Author(s):

Merav Mofaz ◽

Matan Yechezkel ◽

Grace Guan ◽

Margaret L. Brandeau ◽

Tal Patalon ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Booster Dose ◽

Vaccination Campaign ◽

Vaccine Dose ◽

P Value ◽

Booster Vaccine ◽

The Third ◽

Systemic Reactions ◽

Physiological Reactions

AbstractBackgroundThe rapid rise in hospitalizations associated with the Delta-driven COVID-19 resurgence, and the imminent risk of hospital overcrowding, led the Israeli government to initialize a national third (booster) COVID-19 vaccination campaign in early August 2021, offering the BNT162b2 mRNA vaccine to individuals who received their second dose over five months ago. However, the safety of the third (booster) dose has not been fully established yet.ObjectiveEvaluate the short-term, self-reported and physiological reactions to the third BNT162b2 mRNA COVID-19 (booster) vaccine dose.DesignA prospective observational study, in which participants are equipped with a smartwatch and fill in a daily questionnaire via a dedicated mobile application for a period of 21 days, starting seven days before the vaccination.SettingAn Israel-wide third (booster) vaccination campaign.ParticipantsA group of 1,609 (18+ years of age) recipients of at least one dose of the BNT162b2 vaccine between December 20, 2020, and September 15, 2021, out of a larger cohort of 2,912 prospective study participants. 1,344 of the participants were recipients of the third vaccine dose.MeasurementsDaily self-reported questionnaires regarding local and systemic reactions, mood level, stress level, sport duration, and sleep quality. Heart rate, heart rate variability and blood oxygen saturation level were continuously measured by Garmin Vivosmart 4 smartwatches.ResultsThe extent of systemic reactions reported following the third (booster) dose administration is similar to that reported following the second dose (p-value=0.305) and considerably greater than that reported following the first dose (p-value<0.001). Our analyses of self-reported well-being indicators as well as the objective heart rate and heart rate variability measures recorded by the smartwatches further support this finding. Focusing on the third dose, reactions were more apparent in younger participants (p-value<0.01), in women (p-value<0.001), and in participants with no underlying medical conditions (p-value<0.001). Nevertheless, reported reactions and changes in physiological measures returned to their baseline levels within three days from inoculation with the third dose.LimitationsParticipants may not adequately represent the vaccinated population in Israel and elsewhere.ConclusionOur work further supports the safety of a third COVID-19 BNT162b2 mRNA (booster) vaccine dose from both a subjective and an objective perspective, particularly in individuals 65+ years of age and those with underlying medical conditions.Primary funding sourceEuropean Research Council (ERC) project #949850

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Duration of immunity against COVID-19 after vaccination in Indian subcontinent

10.21203/rs.3.rs-1260289/v1 ◽

2022 ◽

Author(s):

Apoorva Munigela ◽

Sasikala M ◽

Gujjarlapudi Deepika ◽

Anand V Kulkarni ◽

Krishna Vemula ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Booster Dose ◽

Indian Subcontinent ◽

Neutralizing Antibody ◽

Health Concern ◽

Mortality Data ◽

Optimal Timing ◽

Cross Sectional ◽

Mortality And Morbidity ◽

Antibody Levels

Abstract Coronavirus disease (COVID-19) continues to be a major health concern leading to substantial mortality and morbidity across the world. Vaccination is effective in reducing the severity and associated mortality. Data pertaining to the duration of immunity, antibody waning and the optimal timing of booster dose administration is limited. In this cross-sectional study, we assessed the antibody levels in healthcare workers who were fully vaccinated after obtaining Institutional ethics committee approval and informed consent. Whole blood was collected and enumeration of S1/S2 neutralizing antibody levels was carried out using LIAISON SARS-COV-2 S1/S2 IgG assay. A total of 1636 individuals who were vaccinated with Covaxin or Covishield were included. Of these, 52% were males with a median age of 29 years. Diabetes and Hypertension was noted in 2.32% (38/1636) and 2.87% (47/1636) of the individuals. Spike neutralizing antibodies were below the detectable range (<15 AU/ml) in 6.0% (98/1636) of the individuals. Decline in neutralizing antibody was seen in 30% of the individuals above 40 years of age with comorbidities (diabetes and hypertension) after 6 months. These individuals may be prioritized for a booster dose at 6 months.

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