The Successful Vaccination of an IVIgG Naive CVID Patient with an mRNA COVID-19 Vaccine.

INTRODUCTION: Different subtypes of vaccines have been developed to help protect populations from COVID-19. Currently, three vaccines have been authorized by the United States Food and Drug Administration for emergency use to combat the COVID-19 pandemic. With COVID-19 vaccination rates increasing, it is important to know whether immunodeficient patients have the capacity to mount an immune response with the available vaccines. CASE REPORT: A 78-year-old female with Common Variable Immunodeficiency and anti-IgA antibodies who is naïve to IVIgG treatment responded positively to a COVID-19 mRNA vaccine. Successful seroconversion was proved by having positive COVID-19 spike protein IgG antibodies weeks after the vaccination. Her recent IgG, IgA, and IgM levels were all significantly reduced. Previously, she had no response to the polysaccharide pneumococcal vaccine, but did maintain titers afterTdap vaccination. DISCUSSION: Immunodeficient patients are a susceptible population during a pandemic. Unfortunately, there is a paucity of research on the infectivity, vaccination, and outcome of these patients during the COVID-19 outbreak. Our patient with CVID was able to respond to protein/toxoid vaccines, but did not respond to polysaccharide pneumococcal vaccine. After inoculation with an mRNA COVID-19 vaccine she was able to create COVID-19 spike protein IgG antibodies.
CONCLUSION: We present a case of successful vaccination to COVID-19 by an mRNA vaccine in an IVIgG naïve CVID patient.

Introduction

In December of 2019 unexplained cases of pneumonia were identified in Wuhan, China. By February 2020 The World Health Organization designated this novel coronaviradae variant, Coronavirus disease 19 (COVID-19) also known as Severe Acute Respiratory Coronavirus Syndrome-2 (SARS-COV-2). This enveloped, positive stranded RNA virus was not previously known to be highly pathogenic in humans until 2002 and 2003 when the first severe acute respiratory syndrome (SARS) was reported. However, by March 2020, the COVID-19 outbreak was declared a global pandemic and the race for an effective vaccine was underway.

There are three vaccines authorized by the Food and Drug Administration (FDA) for emergency use: Pfizer-BioNTech COVID-19 (BNT162b2) vaccine (Pfizer, Inc; Philadelphia, Pennsylvania), Moderna COVID-19 (mRNA-1273) vaccine (ModernaTX, Inc; Cambridge, Massachusetts), and Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc, a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey). Each of these vaccines have been proven effective in the aim to create immunity in light of the massive mortality rates worldwide. However, in our various subsets of immunodeficient patients, it is unknown whether these patients have adequate immune function to mount a protective and lasting response using the vaccines available against COVID-19.

Common variable immune deficiency (CVID), is appropriately named as one of the most prevalent primary immunodeficiencies. Classical presentations of CVID include recurrent infections and hypogammaglobulinemia. Due to the heterogeneity in presentation of this disease, multiple diagnostic criteria have been formulated. Generally, CVID is characterized by low levels of immunoglobulin G (IgG) along with suboptimal levels of immunoglobulin A (IgA) and/or M (IgM), as well as a diminished antibody response to vaccine challenges. In approximately 20% of patients a genetic predisposition can be identified. More likely the disease is due to multifactorial causes such as genetics and environmental factors. Due to the lack of antibody production and subsequent augmented ability in function, the efficacy of vaccines are often compromised. Herein, this case report with a review of the most updated literature aims to highlight the successful vaccination of a CVID patient using an mRNA vaccine.

Case Report

A 78-year-old female with a history of CVID, anti-IgA antibodies, pemphigus vulgaris, allergic rhinitis, asthma, and obstructive sleep apnea presented after vaccination with the Pfizer COVID-19 mRNA vaccine. Her medical history includes an initial diagnosis of Selective IgA deficiency in her 30 s with positive anti-IgA antibodies. In 2004, when she was 61 years old, she started to have an increase in upper respiratory tract and gastrointestinal infections. A repeat immune work up found a global decrease in immunoglobulins with IgG of 444, IgM of 5, and IgA <16. A vaccine challenge with a pneumococcal polysaccharide vaccine and subsequent challenge with a conjugated pneumococcal vaccine showed nonresponse with 0 out of 14 titers protective before vaccination, and 0 out of 14 titers protective after vaccination. Given these findings, her diagnosis was advanced from Selective IgA deficiency to CVID, and she was started on prophylactic antibiotics. At the age of 66 her IgG level dropped to 262, IgM and IgA remained low. The risks and benefits of starting intravenous IgG (IVIgG) were discussed, including her increased risk for anaphylaxis with blood products given her anti-IgA antibodies; however, IVIgG was held, since clinically she had not deteriorated. Given the patients immunodeficiency, we questioned whether the COVID-19 vaccination would be successful. The patient did not previously respond to pneumococcal polysaccharide vaccine, however she had positive tetanus and diphtheria titers- proving successful conversion after protein vaccines. COVID-19 Spike protein IgG antibody (Laboratory Corporation of America Holdings, Burlington, North Carolina) was obtained approximately six weeks after her vaccination series with the Pfizer COVID-19 mRNA vaccine, and was positive, confirming successful vaccination.

Discussion

There is a lack of information regarding COVID-19 infections and vaccinations in immunodeficient patients. Early reports have shown that CVID patients have fared similar to the general population during the COVID-19 pandemic, although larger studies are needed. Generally, CVID patients on IVIgG infusions are protected from certain vaccine preventable diseases since IVIgG products contain specific antibody titers to these diseases, and thus certain vaccination are not required. For novel diseases such as COVID-19, there may not be enough COVID-19 antibodies in donated plasma pools of IVIgG. Furthermore, CVID patients such as our patient described here who are not on IVIgG, still require protection from vaccine preventable diseases. Thus, the efficacy of vaccines in this population is important to characterize.

Our patient was found to have protective titers to diphtheria and tetanus, proving good seroconversion after being inoculated with toxoid protein vaccines. Protection against tetanus and diphtheria toxins involves inoculation with toxoids that activate type 2 helper T cells and B cells to produce specific immunoglobulins that will recognize and neutralize the target toxins in the future.[5,6]

mRNA vaccines are a relatively newer subtype of vaccine. The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine was issued an Emergency Use Authorization (EUA) by the FDA on December 11th, 2020. The vaccination is a two-shot series given intramuscularly 21 days apart. This vaccine encodes a membrane-anchored SARS-CoV-2 full length spike protein. In phase II/III clinical trials the vaccine was found to be 95% effective in preventing symptomatic infections.

The mechanism of action of mRNA vaccines differs from other vaccine subtypes. An mRNA that encodes a target protein, in this case a COVID-19 spike protein, is introduced into the body. mRNAs are usually encased in liposomes or complexed in a manner to prevent degradation and to help the mRNA travel to the cytosolic translational machinery in cells. Once the mRNA is taken up, host cells start producing target proteins on their surface. This process has been shown to prime the adaptive and cellular immune systems. The Pfizer-BioNTech (BNT162b2) vaccine was shown to produce neutralizing antibodies, as well as expand populations and activate specific CD8 + T cells and Type 1 helper CD4 + T cells.

After completing the Pfizer mRNA COVID-19 vaccine series, our patient was positive to the COVID-19 spike protein IgG antibody which confirms this type of vaccine's ability to induce a successful immune response in an IVIgG naive CVID patient. This suggests that CVID patients that respond to protein antigens such as tetanus may be successfully vaccinated with a mRNA vaccine.

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Supplemental material, sj-docx-1-aar-10.1177_21526567211049744 for The Successful Vaccination of an IVIgG Naive CVID Patient with an mRNA COVID-19 Vaccine by Maaz Jalil, John M. Abraham and Robert Hostoffer in Allergy & Rhinology