Finally, an FDA Approval for an Immunization Against COVID-19: Hope on the Horizon

Objective Coronavirus disease 2019 (COVID-19) is a respiratory infection known as severe respiratory acute syndrome coronavirus 2 (SARS-CoV-2). The purpose of this manuscript is to review information leading to the Food and Drug Administration (FDA) approval of the Pfizer-BioNTech COVID-19 Vaccine. Data Sources A literature search was conducted of PubMed and clinicaltrials.gov (August 2018—October 2021) to identify trials related to the FDA approval of Pfizer-BioNTech COVID-19 Vaccine. Study selection and data extraction Trials included are those the FDA deemed significant and accurate enough to be included in the FDA approval process. Information not recognized by the Centers of Disease Control and Prevention (CDC) nor FDA is omitted to not add to further confusion and misinformation. Data synthesis In persons 16 years or older without evidence of prior SARS-CoV-2 infection, a total of 77 COVID-19 cases (0.39%) in the vaccine group from 7 days onward after the second dose vs 833 (4.1%) in the placebo group (Vaccine efficacy 91.1%; 95% confidence interval [CI]: 88.8-93.1). According the CDC definition of severe infection, there were no severe infections in the vaccine group 7 days and onward after the second dose, compared to 31 (0.15%) in the placebo group (Vaccine efficacy 100%; 95% CI: 87.6-100.0). Relevance to Patient Care and Clinical Practice: Reduction of infection by SARS-COV-2 is a top priority in protecting the health of all people and the official approval of the Pfizer-BioNTech vaccination may improve this goal. Conclusions Data available show a high efficacy rate of preventing SARS -CoV-2 with relatively low rates of ADE after full vaccination with Pfizer-BioNTech COVID-19 vaccine.

Safety and Tolerability of an Ad26.RSV.preF-based Vaccine in a Phase 2b Study in Older Adults

Respiratory syncytial virus (RSV) may cause severe lower respiratory tract disease in older adults and there is currently no approved vaccine. We assessed the safety and reactogenicity of an Ad26.RSV.preF-based vaccine in a randomized, double-blind, placebo-controlled Phase 2b proof-of-concept trial in adults aged ≥65 years (CYPRESS; NCT03982199). Prior to the RSV season, participants were randomized 1:1 to receive an Ad26.RSV.preF-based vaccine or placebo. Solicited adverse events (AEs; fatigue, headache, nausea, myalgia, fever, injection site reactions) and unsolicited AEs were assessed from time of vaccination to Day 8 and Day 29, respectively, in a safety subset of 695 participants (vaccine, n=348; placebo, n=347). All participants were followed for serious AEs (SAEs) until the end of the RSV season or 6 months after vaccination, whichever occurred later. A total of 5728 participants were randomized and received vaccine or placebo (n=2891 in each group). In the safety subset, the frequency of solicited AEs and Grade ≥3 solicited AEs was 51.4% and 3.2% in the vaccine group and 20.2% and 0.6% in the placebo group, respectively. The most frequent solicited AEs in the vaccine group were fatigue, myalgia, headache, and injection site pain/tenderness. The rates of unsolicited AEs and Grade ≥3 unsolicited AEs were similar between the vaccine (16.7% and 1.7%) and placebo (14.4% and 1.4%) groups. In the overall study population, the rate of SAEs was similar between groups (vaccine, 4.6%; placebo, 4.7%); none were considered related to the vaccine. The Ad26.RSV.preF-based vaccine was safe and well tolerated in adults aged ≥65 years.

Humoral immune response after COVID-19 infection or BNT162b2 vaccine among older adults: evolution over time and protective thresholds.

INTRODUCTION The objectives of this study were to assess the dynamics of the SARS-CoV-2 anti-RBD IgG response over time among older people after COVID-19 infection or vaccination and its comparison with speculative levels of protection assumed by current data. METHODS From November 2020 to October 2021, we included geriatric patients with serological test results for COVID-19. We considered antibody titre thresholds thought to be high enough to protect against SARS-CoV-2 infection: 141 BAU/ml for protection/vaccine efficacy > 89.3%. Three cohorts are presented. A vaccine group (n=34) that received two BNT162b2/Comirnaty injections 21 days apart, a group of natural COVID-19 infection (n=32) and a third group who contracted COVID-19 less than 15 days after the first BNT162b2/Comirnaty injection (n=17). RESULTS 83 patients were included, the median age was 87 (81-91) years. In the vaccine group at 1 month since the first vaccination, the median BAU/ml with IQR was 620 (217-1874) with 87% of patients above the threshold of 141 BAU/ml. Seven months after the first vaccination the BAU/ml was 30 (19-58) with 9.5% of patients above the threshold of 141 BAU/ml. In the natural COVID-19 infection group, at 1 month since the date of first symptom onset, the median BAU/ml was 798 (325-1320) with 86.7% of patients above the threshold of 141 BAU/ml and fell to 88 (37-385) with 42.9% of patients above the threshold of 141 BAU/ml at 2 months. The natural infection group was vaccinated three months after the infection. Five months after the end of the vaccination cycle the BAU/ml was 2048 (471-4386) with 83.3% of patients above the threshold of 141 BAU/ml. DISCUSSION On the humoral level, this supports the clinical results describing the decrease in vaccine protection over time.

Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon α-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical Trial

IntroductionFunctional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches.Materials and MethodsWe conducted a double-blind randomized placebo-controlled clinical trial to evaluate the safety, immunogenicity, and effect on viral dynamics of a therapeutic vaccine produced with monocyte-derived dendritic cells (MD-DC) loaded with a high dose of heat-inactivated autologous (HIA) HIV-1 in combination with pegylated interferon alpha 2a (IFNα-2a) in people with chronic HIV-1.ResultsTwenty-nine male individuals on successful ART and with CD4+ ≥450 cells/mm3 were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine ~107 MD-DC pulsed with HIA-HIV-1 (1010 HIV RNA copies) (n = 8); (2) vaccine plus three doses of 180 mcg IFNα-2a at weeks 4–6 (n = 6); (3) placebo = saline (n = 7); and (4) placebo plus three doses of 180 mcg IFNα-2a (n = 8). Thereafter, treatment was interrupted (ATI). Vaccines, IFNα-2a, and the administration procedures were safe and well tolerated. All patients’ viral load rebounded during the 12-week ATI period. According to groups, changes in viral set-point between pre-ART and during ATI were not significant. When comparing all groups, there was a tendency in changes in viral set-point between the vaccine group vs. vaccine + IFNα-2a group (>0.5log10p = 0.05). HIV-1-specific T-cell responses (IFN-ƴ Elispot) were higher at baseline in placebo than in the vaccine group (2,259 ± 535 vs. 900 ± 200 SFC/106 PBMC, p = 0.028). A significant difference in the change of specific T-cell responses was only observed at week 4 between vaccine and placebo groups (694 ± 327 vs. 1,718 ± 282 SFC/106 PBMC, p = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INFα-2a administration.DiscussionResults from this study show that intranodally administered DC therapeutic vaccine in combination with IFNα-2a was safe and well-tolerated but had a minimal impact on viral dynamics in HIV-1 chronic infected participants.Clinical Trial Registration(www.ClinicalTrials.gov), identifier NCT02767193

Original Paper: Mixing of Sputnik V and AstraZeneca COVID-19 Vaccines

Background and Aim: The coronavirus disease 2019 (COVID-19) vaccine helps to develop immunity to SARS-CoV-2, the virus that causes COVID-19, in most cases preventing the disease. Although various brands of vaccines work in different modes, all COVID-19 vaccines prompt an immune reaction to make the body remembers how to protect from the virus in the future. The present study aims to evaluate the safety and the immune response for mixing of Sputnik V and AstraZeneca COVID-19 vaccines on mice. Materials and Methods: Our experimental study was performed on mice weighing on average of 20 g, selected by random allocation. The mice were divided into four groups of 12. Group one received a single dose of 0.5 ml Sputnik V COVID-19 vaccine, group two received two doses of 0.5 ml AstraZeneca COVID-19 vaccine, group three received two doses of 0.5 ml Sputnik V together with 0.5 ml AstraZeneca COVID-19 vaccine and group four received two doses of 0.5 ml of 0.9 % NaCl. Results: Our study shows that mixing of Sputnik V and AstraZeneca COVID-19 vaccines is safe and induces good immunity for mice. Conclusion: Mixing of Sputnik V and AstraZeneca COVID-19 vaccines creates no problems and provides good immunity to mice and may be an interesting technique to help to overcome shortcomings of one or the other vaccine. Further toxicity studies are required to assess potential hazards for humans to evaluate the histopathological characteristics.

Single-dose HPV vaccination efficacy among adolescent girls and young women in Kenya (the KEN SHE Study): study protocol for a randomized controlled trial

Background HPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule. Methods We are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15–20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models. Discussion This study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery. Trial registration ClinicalTrials.gov NCT03675256. Registered on September 18, 2018

Mixing of Sputnik V and AstraZeneca COVID-19 vaccines

Background and Aim: The coronavirus disease 2019 (COVID-19) vaccine helps to develop immunity to SARS-CoV-2, the virus that causes COVID-19, in most cases preventing the disease. Although various brands of vaccines work in different modes, all COVID-19 vaccines prompt an immune reaction to make the body remembers how to protect from the virus in the future. The present study aims to evaluate the safety and the immune response for mixing of Sputnik V and AstraZeneca COVID-19 vaccines on mice. Materials and Methods: Our experimental study was performed on mice weighing on average of 20 g, selected by random allocation. The mice were divided into four groups of 12. Group one received a single dose of 0.5 ml Sputnik V COVID-19 vaccine, group two received two doses of 0.5 ml AstraZeneca COVID-19 vaccine, group three received two doses of 0.5 ml Sputnik V together with 0.5 ml AstraZeneca COVID-19 vaccine and group four received two doses of 0.5 ml of 0.9 % NaCl. Results: Our study shows that mixing of Sputnik V and AstraZeneca COVID-19 vaccines is safe and induces good immunity for mice. Conclusion: Mixing of Sputnik V and AstraZeneca COVID-19 vaccines creates no problems and provides good immunity to mice and may be an interesting technique to help to overcome shortcomings of one or the other vaccine. Further toxicity studies are required to assess potential hazards for humans to evaluate the histopathological characteristics.

An Immunogenicity Report for the Comparison between Heterologous and Homologous Prime-Boost Schedules with ChAdOx1-S and BNT162b2 Vaccines

Background: There is a small amount of immunological data on COVID-19 heterologous vaccination schedules in humans. We assessed the immunogenicity of BNT162b2 (Pfizer/BioNTech) administered as a second dose in healthcare workers primed with ChAdOx1-S (Vaxzevria, AstraZeneca). Methods: 197 healthcare workers were included in a monocentric observational study in Foch hospital, France, between June and July 2021. The main outcome was the immunogenicity measured by serum SARS-CoV-2 IgG antibodies. Results: 130 participants received the ChAdOx1-S/BNT vaccine and 67 received the BNT/BNT vaccine. The geometric mean of IgG antibodies was significantly higher in the BNT/BNT vaccine group compared to the ChAdOx1-S/BNT vaccine group, namely 10,734.9, 95% CI (9141.1–12,589.3) vs. 7268.6, 95% CI (6501.3–8128.3), respectively (p < 0.001). However, after adjustment for time duration between the prime and second vaccinations, no significant difference was observed (p = 0.181). A negative correlation between antibody levels and time duration between second dose and serology test was observed for the BNT/BNT vaccine (p < 0.001), which remained significant after adjustment for all covariates (p < 0.001), but not for the ChAdOx1-S/BNT vaccine (p = 0.467). Conclusions: Heterologous and homologous schedules of ChAdOx1-S and BNT vaccines present robust immune responses after the second vaccination. The results observed were equivalent after adjustment for covariates and emphasize the importance of flexibility in deploying mRNA and viral vectored vaccines. Nevertheless, applying the ChAdOx1-S schedule vaccination for the heterologous second dose of BNT was associated with decreased IgG antibody levels compared to the homologous BNT/BNT vaccination.

Efficacy of Two Chlamydia abortus Subcellular Vaccines in a Pregnant Ewe Challenge Model for Ovine Enzootic Abortion

Chlamydia abortus, the aetiological agent of enzootic abortion of ewes, is a major cause of reproductive loss in small ruminants worldwide, accounting for significant economic losses to the farming industry. Disease can be managed through the use of commercial inactivated or live whole organism-based vaccines, although both have limitations particularly in terms of efficacy, safety and disease-associated outbreaks. Here we report a comparison of two experimental vaccines (chlamydial outer membrane complex (COMC) and octyl glucoside (OG)-COMC) based on detergent extracted outer membrane preparations of C. abortus and delivered as prime-boost immunisations, with the commercial live vaccine Cevac® Chlamydia in a pregnant sheep challenge model. No abortions occurred in either experimental vaccine group, while a single abortion occurred in the commercial vaccine group. Bacterial shedding, as a measure of potential risk of transmission of infection to naïve animals, was lowest in the COMC vaccinated group, with reductions of 87.5%, 86.4% and 74% observed for the COMC, OG-COMC and live commercial vaccine groups, respectively, compared to the unvaccinated challenge control group. The results show that the COMC vaccine performed the best and is a safer efficacious alternative to the commercial vaccines. However, to improve commercial viability, future studies should optimise the antigen dose and number of inoculations required.