CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

439

Antibody Responses Decline Post-MVA Vaccination but Persist Following Mpox Infection Joanne Byrne 1 , Aisling Murphy 2 , Alejandro Abner Garcia Leon 1 , Gurvin Saini 1 , Alan Landay 3 , Liem Binh Luong Nguyen 4 , Cathal O'Broin 2 , Mary Horgan 1 , Carlos Mejia-Chew 5 , Corinna Sadlier 6 , Eoghan de Barra 7 , Jane A. O'Halloran 1 , Virginie Gautier 1 , Mallon W. G. Paddy 1 , Eoin R. Feeney 1 , for the All Ireland Infectious Diseases Cohort Study 1 University College Dublin, Dublin, Ireland, 2 St Vincent's Hospital, Dublin, Ireland, 3 University of Texas Medical Branch, Galveston, TX, USA, 4 Cochin Hospital, Paris, France, 5 Mater Misericordiae University Hospital, Dublin, Ireland, 6 Cork University Hospital, Cork, Ireland, 7 Royal College of Surgeons in Ireland, Dublin, Ireland Background: Clade IIb mpox cases have declined globally, likely due to vaccine and post-infection immunity alongside behavioural changes. However, breakthrough infections in vaccinated individuals and reports of reinfections raise questions about immune durability and the need for vaccine booster doses. We aimed to assess the durability of antibody responses following mpox and Modified Vaccinia Ankara (MVA) vaccination. Methods: In a prospective cohort study, we measured plasma IgG titres to Vaccinia virus (VACV) B5 antigen in adults with prior mpox infection, MVA vaccination and historical controls. We used ROC analysis to define the optimum threshold for seropositivity against previously identified true positive and negative samples. Antibody kinetics post-infection or vaccination were analysed with generalised additive mixed models (GAMMs). Multivariable logistic regression identified factors associated with retaining seropositivity post-vaccination. Results are median (IQR) unless specified. Results: A total of 122 participants (100% male, age 36 [33–44] years, 93% Caucasian, 25% people with HIV [PWH], 11% with prior smallpox vaccination) were sampled at 652 (607–700) days post MVA vaccination (72 with a paired sample 378 [237–465] days prior), alongside 13 participants (100% male, aged 33 [31–40] years, 100% Caucasian, 23% PWH, 0% with prior smallpox vaccination) at 747 (677–865) days post mpox (12 with a paired sample 378 [248– 459] prior). Anti-VACVB5 IgG titres >3284 arbitrary units/ml offered 98% (95% CI: 90–100%) sensitivity and 84% (78–95%) specificity to distinguish seropositivity. Of those with prior mpox, 85% (11/13) remained seropositive at 747 (677–865) days (figure). In contrast, the mean predicted VACVB5 titres following MVA vaccination fell below the seropositive threshold at 472 (95% CI: 389–587) days (figure), with only 32% (39/122) remaining seropositive at 652 (607–700) days. PWH had significantly lower odds of retaining seropositivity post-vaccination (OR: 0.17 [95% CI: 0.04–0.54], p =0.01), an association that persisted when adjusted for time since vaccination, age and prior smallpox vaccination, (aOR: 0.19 [95% CI: 0.04–0.61], p =0.01). Conclusions: Post vaccination mpox VACVB5 titres declined significantly over time, with the majority, particularly PWH, losing seropositivity two years post primary vaccination while seropositivity following mpox infection persisted. How these data relate to risk of reinfection or need for booster vaccination remains to be determined.

therefore needed, that can elicit diverse immune responses including broadly neutralizing antibodies (bnAbs). One such class of bnAbs that recognize the CD4-binding site on the HIV-1 Env are the VRC01-class of antibodies. They are derived from the pairing of VH1-2*02 antibody heavy chains with 5-amino acid long CDRL3 expressing light chains and have been isolated from several people living with HIV-1. They not only prevent infection of humanized mice by HIV-1 and of non-human primates by S(H)IV, but also prevented HIV-1 acquisition from susceptible viruses in two phase 3 clinical trials (HVTN 703/704). Hence, VRC01-class antibody elicitation is expected to be essential for an effective HIV-1 vaccine. Methods: We sequentially administered three different Env-derived immunogens in a transgenic mouse model (engineered by the Fred Alt group). Post final immunization, Env+ CD4-BS+ B cells were isolated from spleens of immunized animals and their VH/VL genes sequenced. Selected VH/VL pairs were generated as IgGs, and their binding and neutralizing properties were determined. Results: The elicited antibodies showed accumulated somatic mutations present in human VRC01-class bnAbs and several of them neutralized >30% of heterologous tier 2 viruses. Here, for the first time, we report on ‘prime-boost’ immunization regimens that lead to accelerated development of VRC01-class antibodies capable of neutralizing diverse heterologous, tier 2 HIV-1 viruses. Conclusions: Our study based on the ‘germline-targeting’ vaccination approach, identifies an immunization strategy that rapidly guides the maturation of VRC01-class antibodies towards their cross-neutralizing forms. These efforts will inform the development of phase 1 clinical trials that are focused on the elicitation of broadly neutralizing HIV-1 antibody responses. Evolution and Durability of Mpox-Specific Antibodies Among Vaccinated or Infected Individuals Wang-Da Liu 1 , Tai-Ling Chao 2 , Kai-Hsiang Chen 1 , Hsin-Yun Sun 1 , Guei-Chi Li 1 , Wen-Chun Liu 1 , Cheng-Hsin Wu 1 , Yi-Ching Su 1 , Chia-Yi Lin 1 , Chih-Hao Hung 1 , Sui-Yuan Chang 2 , Chien-Ching Hung 3 1 National Taiwan University Hospital, Taipei, Taiwan, 2 National Taiwan University, Taipei, Taiwan, 3 National Taiwan General Hospital Yunlin, Yunlin, Taiwan Background: While two-dose vaccination using modified vaccinia Ankara Bavarian Nordic (MVA-BN) vaccine has been shown to be effective in preventing Mpox among at-risk populations, data on the short-term durability of serological responses are scarce. Methods: This prospective study enrolled participants planning to undergo 2-dose MVA-BN vaccination or having natural infection to investigate the serological responses after vaccination or infection. Blood samples were collected for determinations of anti-A29 and anti-H3L IgG. We randomly selected 40 participants who had undergone 2-dose vaccination, including 25 people with HIV (PWH) and 15 people without HIV (PWoH), who had completed one-year follow-up with confirmation of seroconversion for at least one of the IgG to determine the neutralizing ability with the use of a plaque reduction neutralizing test (PRNT). Results: 441 participants who had completed 2-dose MVA-BN vaccination were included, including 284 PWH and 157 PWoH. Among PWH, PWoH, and individuals with prior smallpox vaccination, the seroconversion rate for anti-A29 after the second dose of vaccination was 18.2% and 61.2%, 10.9%, respectively, and that for anti-H3L IgG was 65.0%, and 51.6% and 90.6%, respectively. Twelve (18.8%) of 64 and 41 (19.4%) of 211 participants seroreverted for anti-A29 and anti-H3L IgG, respectively, after a 7-month observation. Factors associated with loss of serologic response (seroreversion) included chronic HBV infection (aOR, 4.84; 95% CI, 1.02-23.11) and HCV seropositivity (aOR, 4.84; 95% CI, 1.02-23.11) for anti-A29 IgG, and participants with prior smallpox vaccination (OR, 0.32; 95% CI, 0.11-0.95) for anti-H3L IgG. Of the total of 150 samples examined by PRNT, 103 (68.7%) showed neutralizing ability. The titer of anti-H3L MPXV IgG was modestly correlated with the titer of PRNT (r = 0.38, p < 0.001), while that of anti-A29 MPXV IgG showed no correlation with the titer of PRNT (p=0.14). Of the 16 participants with recent Mpox, 3 (30.0%) and 9 (90.0%) of 10 remained seropositive for anti-A29 and anti-H3L IgG, respectively, at the end of 7 months of follow-up. Conclusions: We found that the anti-A29 and anti-H3L antibodies waned quickly among those have undergone MVA-BN vaccination and even among those with natural infection. In addition, among those tested positive for Mpox specific IgG, the titers of anti-H3L IgG might be a better index for predicting neutralizing ability compared with the titers of anti-A29 IgG.

438

Poster Abstracts

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