COVID-19: Mechanisms of Vaccination and Immunity

Abstract

Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world's population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy.

Keywords: COVID-19; SARS-CoV-2; immunity; nucleic acid tests; serology; vaccination.

Figure 1

Model of immunity induced by infection and vaccination. (A) The world was poorly prepared for the first wave of SARS-CoV-2 spread (blue parts of the curve) [9]. Installed measures for limiting viral spread (*) largely halted further infections (black). Subsequent relaxing of these measures may lead to new waves of viral spreading. Even if this happens several times, it may take significantly more than one year until the majority of individuals become infected and immune. Once available, vaccination (green) will more rapidly induce immunity in a critical percentage of the population, which is necessary for herd immunity. The model scenarios shown are based on current evidence and the assumption that infection and proper vaccines induce immune responses that often protect from (re-) infection. However, there is increasing evidence that immunity to SARS-CoV-2 may only be temporary. This notion is not considered for this Figure because the quantitative importance of waning immunity remains still unknown. (B) In case of the emergence of a novel pathogen, vaccination may start much earlier provided one is prepared, i.e., has ample experience with this family of pathogens, enabling rapid vaccine development and production. Unfortunately, this was not the case for SARS-CoV-2. Not shown is the most favored scenario in which the population is previously vaccinated against a given pathogen, precluding viral spread, which is fortunately the case for immunity to many childhood diseases. Additionally, not shown is the in-between scenario in which a vaccine is available but larger parts of the population are not (yet) vaccinated, which can then be readily achieved.

Figure 1

Model of immunity induced by infection and vaccination. (A) The world was poorly prepared for the first wave of SARS-CoV-2 spread (blue parts of the curve) [9]. Installed measures for limiting viral spread (*) largely halted further infections (black). Subsequent relaxing of these measures may lead to new waves of viral spreading. Even if this happens several times, it may take significantly more than one year until the majority of individuals become infected and immune. Once available, vaccination (green) will more rapidly induce immunity in a critical percentage of the population, which is necessary for herd immunity. The model scenarios shown are based on current evidence and the assumption that infection and proper vaccines induce immune responses that often protect from (re-) infection. However, there is increasing evidence that immunity to SARS-CoV-2 may only be temporary. This notion is not considered for this Figure because the quantitative importance of waning immunity remains still unknown. (B) In case of the emergence of a novel pathogen, vaccination may start much earlier provided one is prepared, i.e., has ample experience with this family of pathogens, enabling rapid vaccine development and production. Unfortunately, this was not the case for SARS-CoV-2. Not shown is the most favored scenario in which the population is previously vaccinated against a given pathogen, precluding viral spread, which is fortunately the case for immunity to many childhood diseases. Additionally, not shown is the in-between scenario in which a vaccine is available but larger parts of the population are not (yet) vaccinated, which can then be readily achieved.

Figure 2

SARS-CoV-2, the spike (S) protein and its receptor binding domain (RBD). (A) Coronaviruses have their name because they are decorated by prominent S proteins (yellow/green). It is the only viral protein that interacts with host cells and is the most diverging protein between different coronaviruses, particularly in its receptor binding domain (RBD, green). RBD binds to angiotensin converting enzyme 2 (ACE2, not shown) on the host’s cell surface. The fusion peptide (FP) fuses with the host cell membrane. Specific antibodies against RBD and FP can neutralize SARS-CoV-2 NTD/CTD, N-/C-terminal domains. (B) RBD is glycosylated and methylated, which may hinder the induction of neutralizing antibodies. In contrast, the receptor interaction site (RIS, green) is not glycosylated.

Figure 3

Antibody-dependent enhancement (ADE) of infection and ADE of inflammation. (A) ADE of infection occurs through antibodies that mediate Fcγ receptor-mediated viral uptake, leading to increased cellular infection. This mechanism may not apply to human SARS coronaviruses since Fcγ receptor-expressing cells unlikely propagate those viruses in patients. (B) ADE of inflammation may occur via Fcγ receptor-mediated virus transfer into endosomes, where viral RNA binds to RNA receptors, triggering inflammatory responses. Alternatively, activatory Fcγ receptors may signal via their ITAM leading to the production of pro-inflammatory cytokines. ADE of inflammation may occur in patients harboring very high viral load in their lungs. ITAM, immunoreceptor tyrosine-based activation motif.

Figure 4

Different types of antibodies and induction of antibodies by infection and vaccination. (A) Antibodies (orange or brown) specific for viral surface proteins can bind to SARS-CoV-2, in contrast to antibodies (pink) specific for the viral nucleoprotein (N), which is not accessible in viable viruses. Antibodies (orange) that bind to RBD are likely neutralizing, as they block the attachment of the virus to its receptor (ACE2) on the surface of host cells (not shown). Most antibodies (brown) binding to other moieties of the spike (S) protein (and antibodies binding to envelope or membrane proteins of SARS-CoV-2; not shown) may not neutralize the virus. +, yes; +/- eventually; - no. (B) Virus-binding antibodies may be induced by infection or vaccine candidates. Virus-like particles displaying RBD (VLP-RBD) have a high likelihood of inducing neutralizing antibodies, provided that they display RBD (green) in a repetitive and thus highly immunogenic manner. Alternatively, RBD-based vaccines may be produced with RBD peptide, or viral vectors, DNA or RNA encoding RBD. The same vaccine types may incorporate alternative antigens such as the full S protein (yellow), which may differ in the degree of immunogenicity but may also be more likely to trigger virus-binding non-neutralizing antibodies, possibly increasing the risk for antibody-dependent enhancement (ADE). Inactivated and live-attenuated viruses (not shown) are expected to have relatively similar antigenic profiles to wild-type virus. +++, strong; ++ intermediate; + weak.