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

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.

A Single Dose SARS-CoV-2 Replicon RNA Vaccine Induces Cellular and Humoral Immune Responses in Simian Immunodeficiency Virus Infected and Uninfected Pigtail Macaques

The ongoing COVID-19 vaccine rollout is critical for reducing SARS-CoV-2 infections, hospitalizations, and deaths worldwide. Unfortunately, massive disparities exist in getting vaccines to vulnerable populations, including people living with HIV. Preliminary studies indicate that COVID-19 mRNA vaccines are safe and immunogenic in people living with HIV that are virally suppressed with potent antiretroviral therapy but may be less efficacious in immunocompromised individuals. This raises the concern that COVID-19 vaccines may be less effective in resource poor settings with limited access to antiretroviral therapy. Here, we evaluated the immunogenicity of a single dose COVID-19 replicon RNA vaccine expressing Spike protein (A.1) from SARS-CoV-2 (repRNA-CoV2S) in immunocompromised, SIV infected and immune competent, naïve pigtail macaques. Moderate vaccine-specific cellular Th1 T-cell responses and binding and neutralizing antibodies were induced by repRNA-CoV2S in SIV infected animals and naïve animals. Furthermore, vaccine immunogenicity was elicited even among the animals with the highest SIV viral burden or lowest peripheral CD4 counts prior to immunization. This study provides evidence that a SARS-CoV-2 repRNA vaccine could be employed to induce strong immunity against COVID-19 in HIV infected and other immunocompromised individuals.

A Single Dose of COVID-19 mRNA Vaccine Induces Airway Immunity in COVID-19 Convalescent Patients

Background: Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Preclinical and clinical studies have shown that a parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior infection compared to two injections of a parenteral vaccine. We investigated whether this was also the case for a COVID-19 mRNA vaccine. Methods: Twenty-three COVID-19 convalescent patients and 20 SARS-CoV-2-naive subjects were vaccinated with respectively one and two doses of the Pfizer-BioNTech COVID-19 RNA vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA to Spike and for their ability to inhibit the binding of Spike to its ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism. Results: In COVID-19 convalescent patients, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after two vaccine doses Conclusion: This study showed that a parenteral booster injection of a COVID-19 RNA vaccine promoted stronger mucosal immune responses in COVID-19 convalescent patients compared to SARS-CoV-2 naive subjects who had received a first vaccine dose.

SARS-CoV2 variant-specific replicating RNA vaccines protect from disease and pathology and reduce viral shedding following challenge with heterologous SARS-CoV2 variants of concern

Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late-2021 with resurgent case numbers in many parts of the world. The emergence of SARS-CoV2 variants of concern (VoC) and evidence that existing vaccines that were designed to protect from the original strains of SARS-CoV-2 may have reduced potency for protection from infection against these VoC is driving continued development of second generation vaccines that can protect against multiple VoC. In this report, we evaluated an alphavirus-based replicating RNA vaccine expressing Spike proteins from the original SARS-CoV-2 Alpha strain and recent VoCs delivered in vivo via a lipid inorganic nanoparticle. Vaccination of both mice and Syrian Golden hamsters showed that vaccination induced potent neutralizing titers against each homologous VoC but reduced neutralization against heterologous challenges. Vaccinated hamsters challenged with homologous SARS-CoV2 variants exhibited complete protection from infection. In addition, vaccinated hamsters challenged with heterologous SARS-CoV-2 variants exhibited significantly reduced shedding of infectious virus. Our data demonstrate that this vaccine platform elicits significant protective immunity against SARS-CoV2 variants and supports continued development of this platform.

646 Acute peri-myocarditis following COVID-19 Pfizer-Biontech vaccine second dose delivery in a male teenager: the good prognosis and unusual ECG

Aims Myocarditis due to COVID-19 mRNA vaccine is an uncommon side effect and the cases seem to have occurred predominantly in young adults under 30 years old. The estimated incidence is 12.6 cases per one million second dose m-RNA vaccine delivery. Methods and results A 17-years-old male was admitted at our department after 18 days COVID-19 Pfizer-BioNtech vaccine second dose delivery with persistent chest pain without respiratory symptoms and, ST-elevation and PR-depression in V3–V6 at the ECG on 3 August 2021. He had no history of heart disease. Physical examination didn’t show anything relevant except for mildly tachycardic heart sounds. In addition blood test showed increase in C-reactive protein, cardiac troponin and N-terminal-pro-B-type natriuretic peptide. An echocardiography showed widespread hypokinesia with reduced left ventricular ejection fraction and highly echogenic pericardium. During the first day cardiac magnetic resonance (CMR) was performed, which showed mild diffuse myocardial oedema on T2-weighted images and T2 mapping and two thin areas of delayed enhancement with non-ischaemic pattern in the lateral wall with involvement of the pericardial sheets confirming peri-myocarditis diagnosis. After 24 h, the ECG showed spread and deep T-waves with QTc prolongation. We performed multiple ECG during the days after to assess morphology changes and QTc. The patient has been asymptomatic for all the hospitalization and on day 7 was performed an echocardiography which describe a full recovery in terms of kinesia and left ventricular ejection fraction. He was discharged asymptomatic with ‘better’ but still negative T-waves and QTc normalization. Two months after discharge CMR was repeated and showed normal left ventricular function without myocardial oedema and pericardial involvement, but with persistent the areas of delayed enhancement with non-ischaemic pattern in the lateral wall. Conclusions In this case report we describe an uncommon COVID-19 m-RNA Vaccine side effect. The first issue is the timing of presentation. On 19 July 2021, AIFA stated that myocarditis is a very uncommon side effect and it usually presents within 14 days after 2nd dose delivery. Our patient was admitted at our department after that time period, probably because we reported the ending part of the myocarditis presented with symptoms of pericarditis; indeed we didn’t report the cardiac troponin plateau but only the descending cardiac troponin wave and we attend a very quick recovery. The second issue in the unique ECG with a very quick evolution (Tako-Tsubo morphology like) which could be characteristic of this kind of Myocarditis. Third, the good progress of the inflammation and quick recovery. Surely is a serious side effect but it’s still less frequent and with better prognosis than COVID-19 Myocarditis. European Medicines Agency (EMA) and Centers for Disease Control and Prevention (CDC) recently stated authorized COVID-19 vaccines advantages are still above risks in all age groups beyond 12 y/o. Why is myocarditis a side effect, Why are adolescent males affected the most and Why is the onset after second dose of m-RNA vaccine are questions still unanswered.