Seroresponse to third doses of SARS-CoV-2 vaccine among patients receiving maintenance dialysis

Given the increased morbidity and mortality from COVID-19 among patients undergoing maintenance dialysis, we examined the seroresponse to an additional dose of SARS-CoV-2 mRNA vaccine, using a hypothesized protective anti-spike protein IgG antibody threshold of 7 based on prior work. Among 395 patients, 384 (97%) had seroresponse ≥7 following administration of the third dose. Among those with suboptimal (peak <7) and minimal (peak <1) seroresponse to an initial mRNA vaccine regimen, the rate of seroresponse ≥7 following a third dose was 97% (36 of 37) and 64% (14 of 22), respectively. Given ongoing high rates of COVID-19 and rapidly waning immunity after an initial vaccine series, we recommend a third mRNA vaccine dose be standard for all patients receiving maintenance dialysis.

Analysis of Neutralization Titers against SARS-CoV-2 in Health-Care Workers Vaccinated with Prime-Boost mRNA–mRNA or Vector–mRNA COVID-19 Vaccines

With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated with either mRNA–mRNA (Comirnaty®, BioNTech-Pfzier, Mainz, Germany/New York, NY, USA, n = 98) or vector-based (Vaxzevria®, Oxford-AstraZeneca, Cambridge, UK) followed by mRNA-based (Comirnaty® or Spikevax®, Moderna, Cambridge, MA, USA) vaccines (n = 16). Vaccine-induced neutralization titers were compared to time-matched, unvaccinated individuals that were infected with SARS-CoV-2 and presented with mild symptoms (n = 38). Significantly higher neutralizing titers were found in both the mRNA–mRNA (ID50: 2525, IQR: 1667–4313) and vector–mRNA (ID50: 4978, IQR: 3364–7508) prime-boost vaccine regimens when compared to SARS-CoV-2 infection (ID50: 401, IQR: 271–792) (p < 0.0001). However, infection with SARS-CoV-2 induced higher titers when compared to a single dose of Vaxzevria® (p = 0.0072). Between mRNA–mRNA and vector–mRNA prime-boost regimens, the vector–mRNA vaccine regimen induced higher neutralization titers (p = 0.0054). Demographically, both age and time between vaccination doses were associated with vaccine-induced neutralization titers (p = 0.02 and p = 0.03, respectively). This warrants further investigation into the optimal time to administer booster vaccination for optimized induction of neutralizing responses. Although anecdotal (n = 3), those with exposure to SARS-CoV-2, either before or after vaccination, demonstrated superior neutralizing titers, which is suggestive of further boosting through viral exposure.

Recent COVID-19 vaccination has minimal effects on the physiological responses to graded exercise in physically active healthy people

Athletes are advised to receive the COVID-19 vaccination to protect them from SARS CoV-2 infection during major competitions. Despite this, many athletes are reluctant to get the COVID-19 vaccine due to concerns that symptoms of vaccinosis may impair athletic performance. OBJECTIVE: To determine the effects of COVID-19 vaccination on the physiological responses to graded exercise. METHODS: Healthy physically active participants completed a 20-minute bout of graded cycling exercise at intensities corresponding to 50, 60, 70 and 80% of the pre-determined V̇O2max before and ~21 days after receiving the COVID-19 vaccine (2 dose Pfizer mRNA or 1 dose Johnson&Johnson). RESULTS: Vaccination had no effect on a large number of physiological responses to exercise measured in blood (e.g. lactate, epinephrine, cortisol) and by respiratory gas exchange (e.g. oxygen uptake, CO2 production, ventilation, respiratory exchange ratio, predicted V̇O2max, ventilatory threshold) (p>0.05). We did, however, find significant elevations in heart rate (~5 bpm) and norepinephrine (p = 0.006 and 0.04, respectively) in response to vigorous (e.g. 70-80% V̇O2max) intensity exercise after vaccination, particularly in those that received the two shot Pfizer mRNA vaccine regimen. These findings held true when compared to demographically matched controls who completed identical bouts of exercise several weeks apart without receiving a vaccine. CONCLUSION: Recent COVID-19 vaccination has minimal effects on the physiological responses to graded exercise in physically active healthy people. The small elevations in cardiovascular and neuroendocrine responses to exercise after the Pfizer mRNA vaccine regimen could have implications for athletes at the elite level and warrants investigation.

Immunogenicity and adverse events of priming with inactivated whole SARS-CoV-2 vaccine (CoronaVac) followed by boosting the ChAdOx1 nCoV-19 vaccine

Background: Responding to SARS-CoV-2 Delta variants escaped the vaccine-induced immunity and waning immunity from the inactivated whole virus vaccine, Thailand recently proposed a heterologous inactivated whole virus vaccine (CoronaVac) viral vector vaccine (ChAdOx1 nCoV-19) prime-boost vaccine regimen(I/V). This study aims to evaluate the immunogenicity and adverse events of this regimen by comparison with homologous CoronaVac, ChAdOx1 nCoV-19, and convalescent serum. Method: Immunogenicity was evaluated by the level of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (S1 subunit) (anti-S RBD). At 2 weeks following the second dosage, a selection of random samples was tested for plaque reduction neutralisation (PRNT) and Pseudotype-Based Microneutralization test (PVNT) against SARS-CoV-2 variants of concern (VOCs). The safety profile of heterologous CoronaVac-ChAdOx1 nCoV-19 prime-boost vaccine regimen was described by interviewing at the 1-month visit. Result: Between April to August 2021,426 participants were included in the study, with 155 obtaining CoronaVac-ChAdOx1 nCoV-19(I/V),32 obtaining homologous CoronaVac(I/I),47 obtaining homologous ChAdOx1 nCoV-19(V/V),169 with history covid-19 infection. Geometric mean titers (GMTs) of anti-S RBD level in the I/V group compare 2wks and 4 wks ( 873.9 vs 639,p=0.00114).At 4 wks, GMTs of anti-S RBD level in I/V group was 639, 95% CI 63-726,and natural infection group 177.3, 95% CI 42-221, and V/V group 211.1, 95% CI 77-152 ,and I/I group 108.2 ,95% CI 77-152 ; all p<0.001).At 2 wks, The GMTs of 50%PRNT of 19 sampling from the I/V group is 434.5, 95% CI 326-579, against wild type and 80.4, 95% CI 56-115, against alpha and 67.4, 95% CI 48-95, against delta and 19.8, 95% CI 14-30, against beta; all p<0.001. At 2 wks, The GMTs of 50%PVNT of 15 sampling from the I/V group is 597.8, 95% CI 368-970, against wild type and 163.9, 95% CI 89-301, against alpha and 157.7, 95% CI 66-378, against delta. The AEs in the I/V schedule were well tolerated and generally unremarkable. Conclusion: The I/V vaccination is a mixed regimen that induced higher immunogenicity and shall be considered for responding to Delta Variants when only inactivated whole virus vaccine and viral vector vaccine was available.

Vaccine-induced, high magnitude HIV Env-specific antibodies with Fc-mediated effector functions are insufficient to protect infant rhesus macaques against oral SHIV infection

Improved access to antiretroviral therapy and antenatal care have significantly reduced in-utero and peri-partum mother-to-child HIV transmission. However, as breastmilk transmission of HIV still occurs at an unacceptable rate there remains a need to develop an effective vaccine for the pediatric population. Previously, we compared different HIV vaccine strategies, intervals, and adjuvants in infant rhesus macaques to optimize the induction of HIV envelope (Env)-specific antibodies with Fc-mediated effector function. Here, we tested the efficacy of an optimized vaccine regimen against oral SHIV acquisition in infant macaques. One group of 12 animals was immunized with 1086.c gp120 protein adjuvanted with 3M-052 in stable emulsion and Modified Vaccinia Ankara (MVA) virus vector expressing 1086.c HIV Env, while the control group (n=12) was immunized only with empty MVA. The first vaccine dose was given within 10 days of birth and booster doses were administered at weeks 6 and 12. The vaccine regimen induced Env-specific plasma IgG antibodies capable of antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Beginning at week 15, infants were exposed orally to escalating doses of heterologous SHIV-1157(QNE)Y173H once a week until infected. Despite the induction of strong Fc-mediated antibody responses, the vaccine regimen did not reduce the risk of infection, time to acquisition, or peak viremia compared to controls. Our results suggest that the non-neutralizing Env-specific antibodies with Fc effector function elicited by this vaccine regimen were insufficient for protection against heterologous oral SHIV infection shortly after the final immunization.

Heterologous SARS-CoV-2 Booster Vaccinations: Preliminary Report

Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-mcg, Janssen Ad26.COV2.S 5x1010 virus particles, or Pfizer-BioNTech BNT162b2 30-mcg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. Results: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 154 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. Conclusion: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

Humoral immune responses to COVID-19 vaccination in people living with HIV on suppressive antiretroviral therapy

ABSTRACTBackgroundOur understanding of COVID-19 vaccine immune responses in people living with HIV (PLWH) remains incomplete.MethodsWe measured circulating antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and ACE2 displacement activities after one and two COVID-19 vaccine doses in 100 adult PLWH and 152 controls.ResultsAll PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525-935) cells/mm3. Median nadir CD4+ T-cell counts were 280 (IQR 120- 490) cells/mm3, and ranged as low as <10 cells/mm3. After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with 0.2 log10 lower anti-RBD antibody concentrations (p=0.03) and ∼7% lower ACE2 displacement activity (p=0.037) after one vaccine dose. Following two vaccine doses however, the association between HIV and weaker responses no longer remained. Rather, older age, a higher burden of chronic health conditions, and having received two ChAdOx1 doses (as opposed to a heterologous or dual mRNA vaccine regimen) were the most significant correlates of weaker humoral responses. No significant association was observed between the most recent or nadir CD4+ T-cell counts and responses to COVID-19 vaccination in PLWH following two vaccine doses.ConclusionsThese results suggest that PLWH whose viral loads are well-controlled on antiretroviral therapy and whose CD4+ T-cell counts are in a healthy range will generally not require a third COVID-19 vaccine dose as part of their initial immunization series, though other factors such as older age, co-morbidities, type of initial vaccine regimen and durability of vaccine responses will influence when this group may benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment and/or who have low CD4+ T-cell counts are needed.