Immune responses and protection against vaginal infection after nasal or vaginal immunization with attenuated herpes simplex virus type‐2

Abstract

SUMMARYWe compared nasal and vaginal immunizations using attenuated herpes simplex virus type-2 (HSV-2) for protection against vaginal infection with wild-type HSV-2. Mice were immunized once intranasally, intravaginally after progestin (DP) treatment, or intravaginally with scari®cation after oestradiol treatment. Compared with vaginal immunizations, nasal immunization did not increase immunoglobulin A (IgA) plasma cell numbers in the vagina or elicit a higher antiviral IgA titre in vaginal secretions. Both types of vaginal immunizations increased the number of immunoglobulin G (IgG) plasma cells in the vagina and the secretion/serum titre ratio of IgG antiviral antibody, indicating local production of virus-speci®c IgG in these groups. Cell-mediated immunity in the vagina, as indicated by memory T-cell secretion of interferon-c (IFN-c) in situ 20 hr after HSV-2 challenge, was essentially equivalent in the vaginally immunized groups but signi®cantly lower in the nasal group, while lymphocyte recruitment to the vagina was similar in all three groups. All three immunizations protected all mice from neurological disease after challenge, but vaginal DP immunization induced the greatest immunity against reinfection of the vaginal epithelium.

Immunity to vaginal herpes simplex virus‐2 infection in B‐cell knockout mice

“…The results of this study are consistent with several earlier reports on the involvement of antibody 11 and T cells/ IFN-c 2,7±10 in immunity against vaginal HSV-2 infection. An early role for antibody is consistent with the presence of neutralizing IgG antibody in vaginal secretions of immunized mice 11 and with widely accepted views concerning the role of secreted antibodies at mucosal surfaces.…”

“…An early role for antibody is consistent with the presence of neutralizing IgG antibody in vaginal secretions of immunized mice 11 and with widely accepted views concerning the role of secreted antibodies at mucosal surfaces. When present, secreted antibodies typically neutralize challenge organisms in the lumen and thereby reduce infection of the epithelium.…”

“…11 In the latter study, puri®ed IgG from vaginal secretions of immunized mice neutralized HSV-2 in vitro when used at its in vivo concentration, and removal of the vaginal secretions from immune mice minutes before vaginal virus challenge increased vaginal infection, suggesting a protective role of secreted antibodies.…”

“…4,5 This immunity involves T lymphocytes, 6±9 interferon-c (IFN-c) 7±10 and possibly immunoglobulin G (IgG) antibody. 11 At present, the signi®cance of antibody for protection of the female genital tract against infection remains controversial. 12 In the particular case of HSV-2, passive transfer of immune serum or anti-HSV monoclonal antibody (mAb) failed to protect against challenge infections, 3,13 and speci®c antibody was not detected in vaginal secretions after a parenteral immunization that produced high antibody titres in serum.…”

Profiles and technological requirements of urogenital probiotics

“…Then, an antigen-specific attack is launched by the adaptive arm of the immune system, consisting of T and B cells, after the microbial antigens have been recognized, processed and presented by antigen presenting cells [181,190,191]. The cross-talk between the innate and the adaptive immune systems, as well as the important role that T and B cells play in conferring long-term immunity in the genital tract, have been discussed previously [181,183,195].…”