Vaccinations for pathogenic organisms have been utilized for decades in both the protection and diagnosis of immunodeficiency patients. Some of these immunodeficient patients may not create an adequate response to vaccination, although some who have significant aberrancies in their immune system may surprisingly create antibodies to immunizations. We present a patient with a large Ig heavy chain deletion (severe deficiency of serum IgG1, IgG2, IgG4, and IgA1) that showed a considerable response (presumably through IgG3) after the Pfizer BioNTech COVID-19 vaccination. This finding in this unique immunodeficient patient warrants further research into alternate antibody response pathways against COVID-19.