The cited study in OP may have a slightly pro-vaccine bias, potentially because two authors have "the potential to receive a share of IP revenue" on a relevant patent, and because one author consults for Moderna. Regardless, the study presents scientifically accurate findings, but in a few places it tries to stretch those into questionable conclusions. For example, the authors write:
> At first glance, the RBD targeting of the vaccine sera neutralization might seem likely to increase susceptibility to viral mutations, but the rest of our results suggest that this MAY not be the case. [4]
So keep that tilt in mind when reading it.
> one might expect targeting a wider variety of places on on the COVID spike protein to result in better immunity against variants
Yes this is good intuition, here are excerpts from other literature illustrating why targeting a wide variety of SARS-COV-2 proteins can provide better immunity. In fact, this reasoning is why ongoing vaccine research is investigating formulations beyond the current solely spike protein focused vaccines. Notably, one shortcoming of the current mRNA vaccine formulations is that they do not induce nucleocapsid (N) protein antibodies - whereas natural infection does.
> The nucleocapsid protein of SARS-CoV-2 has been suggested to be an important target for T cell responses. [1]
> Firstly, this protein contains conserved cross-reactive T cell epitopes that are present among different coronaviruses, suggesting that it could be an ideal target for universal coronavirus vaccines. [1]
> Secondly, the nucleocapsid protein is among the most abundant structural proteins in the coronavirus lifecycle, which may facilitate early antigen presentation and recognition by T cells. [1]
> Previous knowledge on other related coronaviruses and the prompt sequencing of the SARS-CoV-2 genome early in the pandemic allowed to identify the spike (S) and the nucleocapsid (N) structural proteins as major targets of antibodies. [2]
> The surface glycoprotein S, which contains the receptor-binding domain (RBD), has a better known function in immunity and is the leading antigen candidate for vaccine development. N is smaller than S, lacks a glycosylation site, and is extensively used in leading serodiagnostics kits due to its abundant expression during infection and early antibody response but its immunological relevance is less established. [2]
> N forms ribonucleoprotein complexes during the virion assembly process by binding to the viral RNA genome and packing it into long helical structures. Its main function is to regulate viral RNA transcription during replication, promoting the synthesis of its own proteins while interfering with the metabolism, protein translation, and proliferation of the infected host cell. During the process of infection, N dissociates itself from the genome and is exposed to the host immune system, and its high immunogenicity has also prompted its exploration as vaccine target. [2]
> Interestingly, significant protein similarity between SARS-CoV-1, SARS-CoV-2, and other HCoV has been reported for N, including a highly conserved motif in the N-terminal (NT) half of the protein (FYYLGTGP) and relevant immunodominant epitope regions. [2]
> Evidence from multiple experimental studies showing that single RBD point mutations can lead to resistance to neutralizing convalescent plasma from multiple donors suggests that specific single mutants may be able to evade spike-targeting vaccinal immunity in many individuals and rapidly lead to spread of vaccine-resistant SARS-CoV-2. [3]
[1] Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2 https://www.cell.com/cell-reports/pdf/S2211-1247(21)01108-6....
[2] Immunogenicity and crossreactivity of antibodies to the nucleocapsid protein of SARS-CoV-2: utility and limitations in seroprevalence and immunity studies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879156/
[3] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein https://pubmed.ncbi.nlm.nih.gov/33909660/
[4] Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection https://pubmed.ncbi.nlm.nih.gov/34103407/