Memory responses are responsible for protection from reinfection and are essential for effective vaccination. The observation that memory B cell responses do not decay after 6.2 months34,35,42, but instead continue to evolve, is strongly suggestive that individuals who are infected with SARS-CoV-2 could mount a rapid and effective response to the virus upon re-exposure.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
Human neutralizing monoclonal antibodies to the SARS-CoV-2 RBD can be categorized as belonging to four classes on the basis of their target regions on the RBD7. Class-1 and -2 antibodies are among the most potent and also the most abundant antibodies5,6,22,23,26,38. These antibodies target epitopes that overlap or are closely associated with RBD residues K417, E484 and N501. They are frequently sensitive to mutation in these residues and select for K417N, E484K and N501Y mutations in SARS-CoV-2 S expression libraries in yeast and VSV13,16,32. To avert selection and escape, antibody therapies should be composed of combinations of antibodies that target non-overlapping or highly conserved epitopes6,13,14,32,39,40,41,42,43.
The mRNA-based SARS-CoV-2 vaccines are safe and effective, and are being deployed globally to prevent infection and disease. The vaccines elicit antibody responses against the RBD (the major target of neutralizing antibodies22,23,24,25,26,27) in a manner that resembles natural infection. Notably, the neutralizing antibodies produced by mRNA vaccination target the same epitopes as those produced by natural infection. Data are consistent with SARS-CoV-2 S trimers translated from the injected RNA adopting a range of different conformations. Moreover, different individuals immunized with the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccines produce closely related, and nearly identical, antibodies. Whether or not neutralizing antibodies to epitopes other than those involving the RBD are elicited by vaccination remains to be determined.
In 1981, the FDA approved a more sophisticated plasma-derived hepatitis B vaccine for human use. This “inactivated” type of vaccine involved the collection of blood from hepatitis B virus-infected (HBsAg-positive) donors. The pooled blood was subjected to multiple steps to inactive the viral particles that included formaldehyde and heat treatment (or “pasteurization”). Merck Pharmaceuticals manufactured this plasma vaccine as "Heptavax," which was the first commercial hepatitis B virus vaccine. The use of this vaccine was discontinued in 1990 and it is no longer available in the U.S.
Current Recombinant Hepatitis B Vaccines
In 1986, research resulted in a second generation of genetically engineered (or DNA recombinant) hepatitis B vaccines. These new approved vaccines are synthetically prepared and do not contain blood products - it is impossible to get hepatitis B from the new recombinant vaccines that are currently approved in the United States.